![\"Loading..\"](\"//bibbase.org/img/ajax-loader.gif\")
\n\n\n generated by\n \n ![\"bibbase.org\"\n](\"//bibbase.org/img/logo.svg\"\n "\\"BibBase")
\n \n
\n \n\n \n \n \n\n
\n\n\n - \n\n
- \n \n Group by\n \n \n
- \n
- \n Year\n \n
- \n Author\n \n
- \n Type\n \n
- \n Keyword\n \n
- \n Downloads\n \n
\n\n\n - \n \n \n \n \n
- \n
- \n \n Expand/Collapse All\n \n \n
- \n \n Download BibTeX\n \n \n
- \n \n RSS Feed\n \n \n
\n\n \n\n\n \n
\n\n Excellent! Next you can\n create a new website with this list, or\n embed it in an existing web page by copying & pasting\n any of the following snippets.\n\n
\n\n \n JavaScript\n (easiest)\n
\n \n
\n\n PHP\n \n <script src=\"https://bibbase.org/show?bib=https%3A%2F%2Fbibbase.org%2Fzotero%2Fianywong&jsonp=1&jsonp=1\"></script>\n \n \n
\n\n iFrame\n (not recommended)\n \n <?php\n $contents = file_get_contents(\"https://bibbase.org/show?bib=https%3A%2F%2Fbibbase.org%2Fzotero%2Fianywong&jsonp=1\");\n print_r($contents);\n ?>\n \n \n
\n\n \n <iframe src=\"https://bibbase.org/show?bib=https%3A%2F%2Fbibbase.org%2Fzotero%2Fianywong&jsonp=1\"></iframe>\n \n \n For more details see the documention.\n
\n\n\n This is a preview! To use this list on your own web site\n or create a new web site from it,\n create a free account. The file will be added\n and you will be able to edit it in the File Manager.\n We will show you instructions once you've created your account.\n
\n\n \n\n
\n\n To the site owner:
\n\nAction required! Mendeley is changing its\n API. In order to keep using Mendeley with BibBase past April\n 14th, you need to:\n
- \n
- renew the authorization for BibBase on Mendeley, and \n
- update the BibBase URL\n in your page the same way you did when you initially set up\n this page.\n \n
\n \n \n Fix it now\n
\n\n \n \n
\n\n\n \n\n \n \n \n \n\n\n
\n\n \n \n 2024\n \n \n (1)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n \n Generative modeling of biological shapes and images using a probabilistic α-shape sampler.\n \n \n \n \n\n\n \n Winn-Nuñez, E. T.; Witt, H.; Bhaskar, D.; Huang, R. Y.; Reichner, J. S.; Wong, I. Y.; and Crawford, L.\n\n\n \n\n\n\n January 2024.\n \n\n\n\n
\n\n\n\n \n \n![\"Generative](\"//bibbase.org/img/filetypes/link.svg\"\n\t "\\"Paper\\"\n\t")
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@misc{winn-nunez_generative_2024,\n\ttype = {preprint},\n\ttitle = {Generative modeling of biological shapes and images using a probabilistic α-shape sampler},\n\turl = {http://biorxiv.org/lookup/doi/10.1101/2024.01.09.574919},\n\tabstract = {Understanding morphological variation is an important task in many areas of computational biology. Recent studies have focused on developing computational tools for the task of sub-image selection which aims at identifying structural features that best describe the variation between classes of shapes. A major part in assessing the utility of these approaches is to demonstrate their performance on both simulated and real datasets. However, when creating a model for shape statistics, real data can be difficult to access and the sample sizes for these data are often small due to them being expensive to collect. Meanwhile, the current landscape of generative models for shapes has been mostly limited to approaches that use black-box inference---making it difficult to systematically assess the power and calibration of sub-image models. In this paper, we introduce the α-shape sampler: a probabilistic framework for generating realistic 2D and 3D shapes based on probability distributions which can be learned from real data. We demonstrate our framework using proof-of-concept examples and in two real applications in biology where we generate (i) 2D images of healthy and septic neutrophils and (ii) 3D computed tomography (CT) scans of primate mandibular molars. The α-shape sampler R package is open-source and can be downloaded at https://github.com/lcrawlab/ashapesampler.},\n\tlanguage = {en},\n\turldate = {2024-01-12},\n\tauthor = {Winn-Nuñez, Emily T. and Witt, Hadley and Bhaskar, Dhananjay and Huang, Ryan Y. and Reichner, Jonathan S. and Wong, Ian Y. and Crawford, Lorin},\n\tmonth = jan,\n\tyear = {2024},\n\tdoi = {10.1101/2024.01.09.574919},\n}\n\n\n\n Understanding morphological variation is an important task in many areas of computational biology. Recent studies have focused on developing computational tools for the task of sub-image selection which aims at identifying structural features that best describe the variation between classes of shapes. A major part in assessing the utility of these approaches is to demonstrate their performance on both simulated and real datasets. However, when creating a model for shape statistics, real data can be difficult to access and the sample sizes for these data are often small due to them being expensive to collect. Meanwhile, the current landscape of generative models for shapes has been mostly limited to approaches that use black-box inference—making it difficult to systematically assess the power and calibration of sub-image models. In this paper, we introduce the α-shape sampler: a probabilistic framework for generating realistic 2D and 3D shapes based on probability distributions which can be learned from real data. We demonstrate our framework using proof-of-concept examples and in two real applications in biology where we generate (i) 2D images of healthy and septic neutrophils and (ii) 3D computed tomography (CT) scans of primate mandibular molars. The α-shape sampler R package is open-source and can be downloaded at https://github.com/lcrawlab/ashapesampler.\n
\n\n\n\n
\n\n \n \n 2023\n \n \n (4)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n \n Graphene oxide nanosheets augment silk fibroin aerogels for enhanced water stability and oil adsorption.\n \n \n \n \n\n\n \n Machnicki, C. E.; DuBois, E. M.; Fay, M.; Shrestha, S.; Saleeba, Z. S. S. L.; Hruska, A. M.; Ahmed, Z.; Srivastava, V.; Chen, P.; and Wong, I. Y.\n\n\n \n\n\n\n Nanoscale Advances, 5(22): 6078–6092. 2023.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{machnicki_graphene_2023,\n\ttitle = {Graphene oxide nanosheets augment silk fibroin aerogels for enhanced water stability and oil adsorption},\n\tvolume = {5},\n\tissn = {2516-0230},\n\turl = {http://xlink.rsc.org/?DOI=D3NA00350G},\n\tdoi = {10.1039/D3NA00350G},\n\tabstract = {Enhanced intermolecular interactions between silk and graphene oxide nanosheets stabilize nanocomposite aerogels for enhanced water stability and hydrophobic properties, enabing rapid oil adsorption. \n , \n \n Nanocomposite aerogels exhibit high porosity and large interfacial surface areas, enabling enhanced chemical transport and reactivity. Such mesoporous architectures can be prepared by freeze-casting naturally-derived biopolymers such as silk fibroin, but often form mechanically weak structures that degrade in water, which limits their performance under ambient conditions. Adding 2D material fillers such as graphene oxide (GO) or transition metal carbides ( \n e.g. \n MXene) could potentially reinforce these aerogels \n via \n stronger intermolecular interactions with the polymeric binder. Here, we show that freeze-casting of GO nanosheets with silk fibroin results in a highly water-stable, mechanically robust aerogel, with considerably enhanced properties relative to silk-only or silk-MXene aerogels. These silk-GO aerogels exhibit high contact angles with water and are highly water stable. Moreover, aerogels can adsorb up 25–35 times their mass in oil, and can be used robustly for selective oil separation from water. This increased stability may occur due to strengthened intermolecular interactions such as hydrogen bonding, despite the random coil and α-helix conformation of silk fibroin, which is typically more soluble in water. Finally, we show these aerogels can be prepared at scale by freeze-casting on a copper mesh. Ultimately, we envision that these multicomponent aerogels could be widely utilized for molecular separations and environmental sensing, as well as for thermal insulation and electrical conductivity.},\n\tlanguage = {en},\n\tnumber = {22},\n\turldate = {2024-01-09},\n\tjournal = {Nanoscale Advances},\n\tauthor = {Machnicki, Catherine E. and DuBois, Eric M. and Fay, Meg and Shrestha, Snehi and Saleeba, Zachary S. S. L. and Hruska, Alex M. and Ahmed, Zahra and Srivastava, Vikas and Chen, Po-Yen and Wong, Ian Y.},\n\tyear = {2023},\n\tpages = {6078--6092},\n}\n\n\n\n Enhanced intermolecular interactions between silk and graphene oxide nanosheets stabilize nanocomposite aerogels for enhanced water stability and hydrophobic properties, enabing rapid oil adsorption. , Nanocomposite aerogels exhibit high porosity and large interfacial surface areas, enabling enhanced chemical transport and reactivity. Such mesoporous architectures can be prepared by freeze-casting naturally-derived biopolymers such as silk fibroin, but often form mechanically weak structures that degrade in water, which limits their performance under ambient conditions. Adding 2D material fillers such as graphene oxide (GO) or transition metal carbides ( e.g. MXene) could potentially reinforce these aerogels via stronger intermolecular interactions with the polymeric binder. Here, we show that freeze-casting of GO nanosheets with silk fibroin results in a highly water-stable, mechanically robust aerogel, with considerably enhanced properties relative to silk-only or silk-MXene aerogels. These silk-GO aerogels exhibit high contact angles with water and are highly water stable. Moreover, aerogels can adsorb up 25–35 times their mass in oil, and can be used robustly for selective oil separation from water. This increased stability may occur due to strengthened intermolecular interactions such as hydrogen bonding, despite the random coil and α-helix conformation of silk fibroin, which is typically more soluble in water. Finally, we show these aerogels can be prepared at scale by freeze-casting on a copper mesh. Ultimately, we envision that these multicomponent aerogels could be widely utilized for molecular separations and environmental sensing, as well as for thermal insulation and electrical conductivity.\n
\n\n\n\n \n\n \n \n \n \n \n Topological data analysis of spatial patterning in heterogeneous cell populations: clustering and sorting with varying cell-cell adhesion.\n \n \n \n\n\n \n Bhaskar, D.; Zhang, W. Y.; Volkening, A.; Sandstede, B.; and Wong, I. Y.\n\n\n \n\n\n\n NPJ systems biology and applications, 9(1): 43. September 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n
\n\n\n@article{bhaskar_topological_2023,\n\ttitle = {Topological data analysis of spatial patterning in heterogeneous cell populations: clustering and sorting with varying cell-cell adhesion},\n\tvolume = {9},\n\tissn = {2056-7189},\n\tshorttitle = {Topological data analysis of spatial patterning in heterogeneous cell populations},\n\tdoi = {10.1038/s41540-023-00302-8},\n\tabstract = {Different cell types aggregate and sort into hierarchical architectures during the formation of animal tissues. The resulting spatial organization depends (in part) on the strength of adhesion of one cell type to itself relative to other cell types. However, automated and unsupervised classification of these multicellular spatial patterns remains challenging, particularly given their structural diversity and biological variability. Recent developments based on topological data analysis are intriguing to reveal similarities in tissue architecture, but these methods remain computationally expensive. In this article, we show that multicellular patterns organized from two interacting cell types can be efficiently represented through persistence images. Our optimized combination of dimensionality reduction via autoencoders, combined with hierarchical clustering, achieved high classification accuracy for simulations with constant cell numbers. We further demonstrate that persistence images can be normalized to improve classification for simulations with varying cell numbers due to proliferation. Finally, we systematically consider the importance of incorporating different topological features as well as information about each cell type to improve classification accuracy. We envision that topological machine learning based on persistence images will enable versatile and robust classification of complex tissue architectures that occur in development and disease.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {NPJ systems biology and applications},\n\tauthor = {Bhaskar, Dhananjay and Zhang, William Y. and Volkening, Alexandria and Sandstede, Björn and Wong, Ian Y.},\n\tmonth = sep,\n\tyear = {2023},\n\tpmid = {37709793},\n\tpages = {43},\n}\n\n\n\n Different cell types aggregate and sort into hierarchical architectures during the formation of animal tissues. The resulting spatial organization depends (in part) on the strength of adhesion of one cell type to itself relative to other cell types. However, automated and unsupervised classification of these multicellular spatial patterns remains challenging, particularly given their structural diversity and biological variability. Recent developments based on topological data analysis are intriguing to reveal similarities in tissue architecture, but these methods remain computationally expensive. In this article, we show that multicellular patterns organized from two interacting cell types can be efficiently represented through persistence images. Our optimized combination of dimensionality reduction via autoencoders, combined with hierarchical clustering, achieved high classification accuracy for simulations with constant cell numbers. We further demonstrate that persistence images can be normalized to improve classification for simulations with varying cell numbers due to proliferation. Finally, we systematically consider the importance of incorporating different topological features as well as information about each cell type to improve classification accuracy. We envision that topological machine learning based on persistence images will enable versatile and robust classification of complex tissue architectures that occur in development and disease.\n
\n\n\n\n \n\n \n \n \n \n \n \n Dynamic Tumor Perfusion and Real-Time Monitoring in a Multiplexed 3D Printed Microdevice.\n \n \n \n \n\n\n \n Markoski, A.; Wong, I. Y.; and Borenstein, J. T.\n\n\n \n\n\n\n In Garcia-Cordero, J. L.; and Revzin, A., editor(s), Microfluidic Systems for Cancer Diagnosis, volume 2679, pages 287–304. Springer US, New York, NY, 2023.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@incollection{garcia-cordero_dynamic_2023,\n\taddress = {New York, NY},\n\ttitle = {Dynamic {Tumor} {Perfusion} and {Real}-{Time} {Monitoring} in a {Multiplexed} {3D} {Printed} {Microdevice}},\n\tvolume = {2679},\n\tisbn = {9781071632703 9781071632710},\n\turl = {https://link.springer.com/10.1007/978-1-0716-3271-0_20},\n\tabstract = {Stereolithography based additive manufacturing (“3D printing”) has become a useful tool for the development of novel microfluidic in vitro platforms. This method of manufacturing can reduce production time while allowing for rapid design iteration and complex monolithic structures. The platform described in this chapter has been designed for the capture and evaluation of cancer spheroids in perfusion. Spheroids are created in 3D Petri dishes, stained, and loaded into these 3D printed devices and imaged over time under flow conditions. This design allows for active perfusion into complex 3D cellular constructs resulting in longer viability while providing results which better mimic in vivo conditions compared to traditional monolayer static culture.},\n\tlanguage = {en},\n\turldate = {2023-06-15},\n\tbooktitle = {Microfluidic {Systems} for {Cancer} {Diagnosis}},\n\tpublisher = {Springer US},\n\tauthor = {Markoski, Alex and Wong, Ian Y. and Borenstein, Jeffrey T.},\n\teditor = {Garcia-Cordero, Jose L. and Revzin, Alexander},\n\tyear = {2023},\n\tdoi = {10.1007/978-1-0716-3271-0_20},\n\tpages = {287--304},\n}\n\n\n\n Stereolithography based additive manufacturing (“3D printing”) has become a useful tool for the development of novel microfluidic in vitro platforms. This method of manufacturing can reduce production time while allowing for rapid design iteration and complex monolithic structures. The platform described in this chapter has been designed for the capture and evaluation of cancer spheroids in perfusion. Spheroids are created in 3D Petri dishes, stained, and loaded into these 3D printed devices and imaged over time under flow conditions. This design allows for active perfusion into complex 3D cellular constructs resulting in longer viability while providing results which better mimic in vivo conditions compared to traditional monolayer static culture.\n
\n\n\n\n \n\n \n \n \n \n \n \n Mechanobiology of Collective Cell Migration in 3D Microenvironments.\n \n \n \n \n\n\n \n Hruska, A. M.; Yang, H.; Leggett, S. E.; Guo, M.; and Wong, I. Y.\n\n\n \n\n\n\n In Wong, I. Y.; and Dawson, M. R., editor(s), Engineering and Physical Approaches to Cancer, pages 1–32. Springer International Publishing, Cham, 2023.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 5 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 5 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@incollection{wong_mechanobiology_2023,\n\taddress = {Cham},\n\ttitle = {Mechanobiology of {Collective} {Cell} {Migration} in {3D} {Microenvironments}},\n\tisbn = {9783031228018 9783031228025},\n\turl = {https://link.springer.com/10.1007/978-3-031-22802-5_1},\n\tabstract = {Tumor cells invade individually or in groups, mediated by mechanical interactions between cells and their surrounding matrix. These multicellular dynamics are reminiscent of leader-follower coordination and epithelial-mesenchymal transitions (EMT) in tissue development, which may occur via dysregulation of associated molecular or physical mechanisms. However, it remains challenging to elucidate such phenotypic heterogeneity and plasticity without precision measurements of single-cell behavior. The convergence of technological developments in live cell imaging, biophysical measurements, and 3D biomaterials is highly promising to reveal how tumor cells cooperate in aberrant microenvironments. Here, we highlight new results in collective migration from the perspective of cancer biology and bioengineering. First, we review the biology of collective cell migration. Next, we consider physics-inspired analyses based on order parameters and phase transitions. Further, we examine the interplay of metabolism and phenotypic heterogeneity in collective migration. We then review the extracellular matrix and new modalities for mechanical characterization of 3D biomaterials. We also explore epithelial-mesenchymal plasticity and implications for tumor progression. Finally, we speculate on future directions for integrating mechanobiology and cancer cell biology to elucidate collective migration.},\n\tlanguage = {en},\n\turldate = {2023-04-12},\n\tbooktitle = {Engineering and {Physical} {Approaches} to {Cancer}},\n\tpublisher = {Springer International Publishing},\n\tauthor = {Hruska, Alex M. and Yang, Haiqian and Leggett, Susan E. and Guo, Ming and Wong, Ian Y.},\n\teditor = {Wong, Ian Y. and Dawson, Michelle R.},\n\tyear = {2023},\n\tdoi = {10.1007/978-3-031-22802-5_1},\n\tpages = {1--32},\n}\n\n\n\n Tumor cells invade individually or in groups, mediated by mechanical interactions between cells and their surrounding matrix. These multicellular dynamics are reminiscent of leader-follower coordination and epithelial-mesenchymal transitions (EMT) in tissue development, which may occur via dysregulation of associated molecular or physical mechanisms. However, it remains challenging to elucidate such phenotypic heterogeneity and plasticity without precision measurements of single-cell behavior. The convergence of technological developments in live cell imaging, biophysical measurements, and 3D biomaterials is highly promising to reveal how tumor cells cooperate in aberrant microenvironments. Here, we highlight new results in collective migration from the perspective of cancer biology and bioengineering. First, we review the biology of collective cell migration. Next, we consider physics-inspired analyses based on order parameters and phase transitions. Further, we examine the interplay of metabolism and phenotypic heterogeneity in collective migration. We then review the extracellular matrix and new modalities for mechanical characterization of 3D biomaterials. We also explore epithelial-mesenchymal plasticity and implications for tumor progression. Finally, we speculate on future directions for integrating mechanobiology and cancer cell biology to elucidate collective migration.\n
\n\n\n\n
\n\n \n \n 2022\n \n \n (4)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n \n Stem cell phenotype predicts therapeutic response in glioblastomas with MGMT promoter methylation.\n \n \n \n \n\n\n \n Lakis, N. S.; Brodsky, A. S.; Karashchuk, G.; Audesse, A. J.; Yang, D.; Sturtevant, A.; Lombardo, K.; Wong, I. Y.; Webb, A. E.; and Anthony, D. C.\n\n\n \n\n\n\n Acta Neuropathologica Communications, 10(1): 159. November 2022.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n\n
\n\n\n@article{lakis_stem_2022,\n\ttitle = {Stem cell phenotype predicts therapeutic response in glioblastomas with {MGMT} promoter methylation},\n\tvolume = {10},\n\tissn = {2051-5960},\n\turl = {https://doi.org/10.1186/s40478-022-01459-9},\n\tdoi = {10.1186/s40478-022-01459-9},\n\tabstract = {A growing body of evidence supports the presence of a population of cells in glioblastoma (GBM) with a stem cell-like phenotype which shares certain biological markers with adult neural stem cells, including expression of SOX2, CD133 (PROM1), and NES (nestin). This study was designed to determine the relationship between the expression of these stem cell markers and the clinical outcome in GBM patients. We quantified the intensity of expression of the proteins CD133 and SOX2 by immunohistochemistry (IHC) in a cohort of 86 patients with IDH-wildtype GBM, and evaluated patient outcomes using Kaplan–Meier and Cox proportional hazards analysis. In our patients, MGMT promoter methylation status and age were predictors of overall survival and progression free survival. The levels of SOX2 and CD133 were not associated with outcome in univariate analysis; however, stratification of tumors based on low or high levels of CD133 or SOX2 expression revealed that MGMT methylation was a predictor of progression-free survival and overall survival only for tumors with high levels of expression of CD133 or SOX2. Tumors with low levels of expression of CD133 or SOX2 did not show any relationship between MGMT methylation and survival. This relationship between MGMT and stem cell markers was confirmed in a second patient cohort, the TCGA dataset. Our results show that stratification of GBM by the level of expression of CD133 and SOX2 improved the prognostic power of MGMT promoter methylation status, identifying a low-expressing group in which the clinical outcome is not associated with MGMT promoter methylation status, and a high-expressing group in which the outcome was strongly associated with MGMT promoter methylation status. These findings support the concept that the presence of a high stem cell phenotype in GBM, as marked by expression of SOX2 or CD133, may be associated with the clinical response to treatment.},\n\tnumber = {1},\n\turldate = {2022-11-04},\n\tjournal = {Acta Neuropathologica Communications},\n\tauthor = {Lakis, Nelli S. and Brodsky, Alexander S. and Karashchuk, Galina and Audesse, Amanda J. and Yang, Dongfang and Sturtevant, Ashlee and Lombardo, Kara and Wong, Ian Y. and Webb, Ashley E. and Anthony, Douglas C.},\n\tmonth = nov,\n\tyear = {2022},\n\tkeywords = {CD133, Cancer stem cells, Glioblastoma, MGMT, SOX2},\n\tpages = {159},\n}\n\n\n\n A growing body of evidence supports the presence of a population of cells in glioblastoma (GBM) with a stem cell-like phenotype which shares certain biological markers with adult neural stem cells, including expression of SOX2, CD133 (PROM1), and NES (nestin). This study was designed to determine the relationship between the expression of these stem cell markers and the clinical outcome in GBM patients. We quantified the intensity of expression of the proteins CD133 and SOX2 by immunohistochemistry (IHC) in a cohort of 86 patients with IDH-wildtype GBM, and evaluated patient outcomes using Kaplan–Meier and Cox proportional hazards analysis. In our patients, MGMT promoter methylation status and age were predictors of overall survival and progression free survival. The levels of SOX2 and CD133 were not associated with outcome in univariate analysis; however, stratification of tumors based on low or high levels of CD133 or SOX2 expression revealed that MGMT methylation was a predictor of progression-free survival and overall survival only for tumors with high levels of expression of CD133 or SOX2. Tumors with low levels of expression of CD133 or SOX2 did not show any relationship between MGMT methylation and survival. This relationship between MGMT and stem cell markers was confirmed in a second patient cohort, the TCGA dataset. Our results show that stratification of GBM by the level of expression of CD133 and SOX2 improved the prognostic power of MGMT promoter methylation status, identifying a low-expressing group in which the clinical outcome is not associated with MGMT promoter methylation status, and a high-expressing group in which the outcome was strongly associated with MGMT promoter methylation status. These findings support the concept that the presence of a high stem cell phenotype in GBM, as marked by expression of SOX2 or CD133, may be associated with the clinical response to treatment.\n
\n\n\n\n \n\n \n \n \n \n \n The need for speed: Migratory cells in tight spaces boost their molecular clock.\n \n \n \n\n\n \n Bhaskar, D.; Hruska, A. M.; and Wong, I. Y.\n\n\n \n\n\n\n Cell Systems, 13(7): 509–511. July 2022.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n
\n\n\n@article{bhaskar_need_2022,\n\ttitle = {The need for speed: {Migratory} cells in tight spaces boost their molecular clock},\n\tvolume = {13},\n\tissn = {2405-4720},\n\tshorttitle = {The need for speed},\n\tdoi = {10.1016/j.cels.2022.06.002},\n\tabstract = {Cells migrating in spatial confinement exhibit higher intracellular calcium levels, which increases the oscillation frequency of a "molecular clock" that synchronizes guanine nucleotide exchange factor GEF-H1 and microtubule polymerization for more frequent bursts of speed.},\n\tlanguage = {eng},\n\tnumber = {7},\n\tjournal = {Cell Systems},\n\tauthor = {Bhaskar, Dhananjay and Hruska, Alex M. and Wong, Ian Y.},\n\tmonth = jul,\n\tyear = {2022},\n\tpmid = {35863324},\n\tpages = {509--511},\n}\n\n\n\n Cells migrating in spatial confinement exhibit higher intracellular calcium levels, which increases the oscillation frequency of a \"molecular clock\" that synchronizes guanine nucleotide exchange factor GEF-H1 and microtubule polymerization for more frequent bursts of speed.\n
\n\n\n\n \n\n \n \n \n \n \n \n Somatic mutations in collagens are associated with a distinct tumor environment and overall survival in gastric cancer.\n \n \n \n \n\n\n \n Brodsky, A. S.; Khurana, J.; Guo, K. S.; Wu, E. Y.; Yang, D.; Siddique, A. S.; Wong, I. Y.; Gamsiz Uzun, E. D.; and Resnick, M. B.\n\n\n \n\n\n\n BMC Cancer, 22(1): 139. February 2022.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{brodsky_somatic_2022,\n\ttitle = {Somatic mutations in collagens are associated with a distinct tumor environment and overall survival in gastric cancer},\n\tvolume = {22},\n\tissn = {1471-2407},\n\turl = {https://bmccancer.biomedcentral.com/articles/10.1186/s12885-021-09136-1},\n\tdoi = {10.1186/s12885-021-09136-1},\n\tabstract = {Abstract \n \n Background \n Gastric cancer is a heterogeneous disease with poorly understood genetic and microenvironmental factors. Mutations in collagen genes are associated with genetic diseases that compromise tissue integrity, but their role in tumor progression has not been extensively reported. Aberrant collagen expression has been long associated with malignant tumor growth, invasion, chemoresistance, and patient outcomes. We hypothesized that somatic mutations in collagens could functionally alter the tumor extracellular matrix. \n \n \n Methods \n We used publicly available datasets including The Tumor Cancer Genome Atlas (TCGA) to interrogate somatic mutations in collagens in stomach adenocarcinomas. To demonstrate that collagens were significantly mutated above background mutation rates, we used a moderated Kolmogorov-Smirnov test along with combination analysis with a bootstrap approach to define the background accounting for mutation rates. Association between mutations and clinicopathological features was evaluated by Fisher or chi-squared tests. Association with overall survival was assessed by Kaplan-Meier and the Cox-Proportional Hazards Model. Gene Set Enrichment Analysis was used to interrogate pathways. Immunohistochemistry and in situ hybridization tested expression of COL7A1 in stomach tumors. \n \n \n Results \n In stomach adenocarcinomas, we identified individual collagen genes and sets of collagen genes harboring somatic mutations at a high frequency compared to background in both microsatellite stable, and microsatellite instable tumors in TCGA. Many of the missense mutations resemble the same types of loss of function mutations in collagenopathies that disrupt tissue formation and destabilize cells providing guidance to interpret the somatic mutations. We identified combinations of somatic mutations in collagens associated with overall survival, with a distinctive tumor microenvironment marked by lower matrisome expression and immune cell signatures. Truncation mutations were strongly associated with improved outcomes suggesting that loss of expression of secreted collagens impact tumor progression and treatment response. Germline collagenopathy variants guided interpretation of impactful somatic mutations on tumors. \n \n \n Conclusions \n These observations highlight that many collagens, expressed in non-physiologically relevant conditions in tumors, harbor impactful somatic mutations in tumors, suggesting new approaches for classification and therapy development in stomach cancer. In sum, these findings demonstrate how classification of tumors by collagen mutations identified strong links between specific genotypes and the tumor environment.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2022-06-01},\n\tjournal = {BMC Cancer},\n\tauthor = {Brodsky, Alexander S. and Khurana, Jay and Guo, Kevin S. and Wu, Elizabeth Y. and Yang, Dongfang and Siddique, Ayesha S. and Wong, Ian Y. and Gamsiz Uzun, Ece D. and Resnick, Murray B.},\n\tmonth = feb,\n\tyear = {2022},\n\tpages = {139},\n}\n\n\n\n Abstract Background Gastric cancer is a heterogeneous disease with poorly understood genetic and microenvironmental factors. Mutations in collagen genes are associated with genetic diseases that compromise tissue integrity, but their role in tumor progression has not been extensively reported. Aberrant collagen expression has been long associated with malignant tumor growth, invasion, chemoresistance, and patient outcomes. We hypothesized that somatic mutations in collagens could functionally alter the tumor extracellular matrix. Methods We used publicly available datasets including The Tumor Cancer Genome Atlas (TCGA) to interrogate somatic mutations in collagens in stomach adenocarcinomas. To demonstrate that collagens were significantly mutated above background mutation rates, we used a moderated Kolmogorov-Smirnov test along with combination analysis with a bootstrap approach to define the background accounting for mutation rates. Association between mutations and clinicopathological features was evaluated by Fisher or chi-squared tests. Association with overall survival was assessed by Kaplan-Meier and the Cox-Proportional Hazards Model. Gene Set Enrichment Analysis was used to interrogate pathways. Immunohistochemistry and in situ hybridization tested expression of COL7A1 in stomach tumors. Results In stomach adenocarcinomas, we identified individual collagen genes and sets of collagen genes harboring somatic mutations at a high frequency compared to background in both microsatellite stable, and microsatellite instable tumors in TCGA. Many of the missense mutations resemble the same types of loss of function mutations in collagenopathies that disrupt tissue formation and destabilize cells providing guidance to interpret the somatic mutations. We identified combinations of somatic mutations in collagens associated with overall survival, with a distinctive tumor microenvironment marked by lower matrisome expression and immune cell signatures. Truncation mutations were strongly associated with improved outcomes suggesting that loss of expression of secreted collagens impact tumor progression and treatment response. Germline collagenopathy variants guided interpretation of impactful somatic mutations on tumors. Conclusions These observations highlight that many collagens, expressed in non-physiologically relevant conditions in tumors, harbor impactful somatic mutations in tumors, suggesting new approaches for classification and therapy development in stomach cancer. In sum, these findings demonstrate how classification of tumors by collagen mutations identified strong links between specific genotypes and the tumor environment.\n
\n\n\n\n \n\n \n \n \n \n \n \n Reciprocity of Cell Mechanics with Extracellular Stimuli: Emerging Opportunities for Translational Medicine.\n \n \n \n \n\n\n \n Li, Y.; Wong, I. Y.; and Guo, M.\n\n\n \n\n\n\n Small,2107305. March 2022.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{li_reciprocity_2022,\n\ttitle = {Reciprocity of {Cell} {Mechanics} with {Extracellular} {Stimuli}: {Emerging} {Opportunities} for {Translational} {Medicine}},\n\tissn = {1613-6810, 1613-6829},\n\tshorttitle = {Reciprocity of {Cell} {Mechanics} with {Extracellular} {Stimuli}},\n\turl = {https://onlinelibrary.wiley.com/doi/10.1002/smll.202107305},\n\tdoi = {10.1002/smll.202107305},\n\tabstract = {Human cells encounter dynamic mechanical cues in healthy and diseased tissues, which regulate their molecular and biophysical phenotype, including intracellular mechanics as well as force generation. Recent developments in bio/nanomaterials and microfluidics permit exquisitely sensitive measurements of cell mechanics, as well as spatiotemporal control over external mechanical stimuli to regulate cell behavior. In this review, the mechanobiology of cells interacting bidirectionally with their surrounding microenvironment, and the potential relevance for translational medicine are considered. Key fundamental concepts underlying the mechanics of living cells as well as the extracelluar matrix are first introduced. Then the authors consider case studies based on 1) microfluidic measurements of nonadherent cell deformability, 2) cell migration on micro/nano-topographies, 3) traction measurements of cells in three-dimensional (3D) matrix, 4) mechanical programming of organoid morphogenesis, as well as 5) active mechanical stimuli for potential therapeutics. These examples highlight the promise of disease diagnosis using mechanical measurements, a systems-level understanding linking molecular with biophysical phenotype, as well as therapies based on mechanical perturbations. This review concludes with a critical discussion of these emerging technologies and future directions at the interface of engineering, biology, and medicine.},\n\tlanguage = {en},\n\turldate = {2022-06-01},\n\tjournal = {Small},\n\tauthor = {Li, Yiwei and Wong, Ian Y. and Guo, Ming},\n\tmonth = mar,\n\tyear = {2022},\n\tpages = {2107305},\n}\n\n\n\n Human cells encounter dynamic mechanical cues in healthy and diseased tissues, which regulate their molecular and biophysical phenotype, including intracellular mechanics as well as force generation. Recent developments in bio/nanomaterials and microfluidics permit exquisitely sensitive measurements of cell mechanics, as well as spatiotemporal control over external mechanical stimuli to regulate cell behavior. In this review, the mechanobiology of cells interacting bidirectionally with their surrounding microenvironment, and the potential relevance for translational medicine are considered. Key fundamental concepts underlying the mechanics of living cells as well as the extracelluar matrix are first introduced. Then the authors consider case studies based on 1) microfluidic measurements of nonadherent cell deformability, 2) cell migration on micro/nano-topographies, 3) traction measurements of cells in three-dimensional (3D) matrix, 4) mechanical programming of organoid morphogenesis, as well as 5) active mechanical stimuli for potential therapeutics. These examples highlight the promise of disease diagnosis using mechanical measurements, a systems-level understanding linking molecular with biophysical phenotype, as well as therapies based on mechanical perturbations. This review concludes with a critical discussion of these emerging technologies and future directions at the interface of engineering, biology, and medicine.\n
\n\n\n\n
\n\n \n \n 2021\n \n \n (3)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n \n The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems.\n \n \n \n \n\n\n \n Leggett, S. E.; Hruska, A. M.; Guo, M.; and Wong, I. Y.\n\n\n \n\n\n\n Cell Communication and Signaling, 19(1): 32. December 2021.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{leggett_epithelial-mesenchymal_2021,\n\ttitle = {The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems},\n\tvolume = {19},\n\tissn = {1478-811X},\n\turl = {https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00713-2},\n\tdoi = {10.1186/s12964-021-00713-2},\n\tabstract = {Abstract \n The epithelial-mesenchymal transition (EMT) is intrinsically linked to alterations of the intracellular cytoskeleton and the extracellular matrix. After EMT, cells acquire an elongated morphology with front/back polarity, which can be attributed to actin-driven protrusion formation as well as the gain of vimentin expression. Consequently, cells can deform and remodel the surrounding matrix in order to facilitate local invasion. In this review, we highlight recent bioengineering approaches to elucidate EMT and functional changes in the cytoskeleton. First, we review transitions between multicellular clusters and dispersed individuals on planar surfaces, which often exhibit coordinated behaviors driven by leader cells and EMT. Second, we consider the functional role of vimentin, which can be probed at subcellular length scales and within confined spaces. Third, we discuss the role of topographical patterning and EMT via a contact guidance like mechanism. Finally, we address how multicellular clusters disorganize and disseminate in 3D matrix. These new technologies enable controlled physical microenvironments and higher-resolution spatiotemporal measurements of EMT at the single cell level. In closing, we consider future directions for the field and outstanding questions regarding EMT and the cytoskeleton for human cancer progression.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2022-06-01},\n\tjournal = {Cell Communication and Signaling},\n\tauthor = {Leggett, Susan E. and Hruska, Alex M. and Guo, Ming and Wong, Ian Y.},\n\tmonth = dec,\n\tyear = {2021},\n\tpages = {32},\n}\n\n\n\n Abstract The epithelial-mesenchymal transition (EMT) is intrinsically linked to alterations of the intracellular cytoskeleton and the extracellular matrix. After EMT, cells acquire an elongated morphology with front/back polarity, which can be attributed to actin-driven protrusion formation as well as the gain of vimentin expression. Consequently, cells can deform and remodel the surrounding matrix in order to facilitate local invasion. In this review, we highlight recent bioengineering approaches to elucidate EMT and functional changes in the cytoskeleton. First, we review transitions between multicellular clusters and dispersed individuals on planar surfaces, which often exhibit coordinated behaviors driven by leader cells and EMT. Second, we consider the functional role of vimentin, which can be probed at subcellular length scales and within confined spaces. Third, we discuss the role of topographical patterning and EMT via a contact guidance like mechanism. Finally, we address how multicellular clusters disorganize and disseminate in 3D matrix. These new technologies enable controlled physical microenvironments and higher-resolution spatiotemporal measurements of EMT at the single cell level. In closing, we consider future directions for the field and outstanding questions regarding EMT and the cytoskeleton for human cancer progression.\n
\n\n\n\n \n\n \n \n \n \n \n \n 3D Printed Monolithic Device for the Microfluidic Capture, Perfusion, and Analysis of Multicellular Spheroids.\n \n \n \n \n\n\n \n Markoski, A.; Wong, I. Y.; and Borenstein, J. T.\n\n\n \n\n\n\n Frontiers in Medical Technology, 3: 646441. April 2021.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{markoski_3d_2021,\n\ttitle = {{3D} {Printed} {Monolithic} {Device} for the {Microfluidic} {Capture}, {Perfusion}, and {Analysis} of {Multicellular} {Spheroids}},\n\tvolume = {3},\n\tissn = {2673-3129},\n\turl = {https://www.frontiersin.org/articles/10.3389/fmedt.2021.646441/full},\n\tdoi = {10.3389/fmedt.2021.646441},\n\tabstract = {Microfluidic systems for the analysis of tissue models of cancer and other diseases are rapidly emerging, with an increasing recognition that perfusion is required to recapitulate critical aspects of the \n in vivo \n microenvironment. Here we report on the first application of 3D printing for the fabrication of monolithic devices suitable for capturing and imaging tumor spheroids under dynamic perfusion flow. Resolution of the printing process has been refined to a level sufficient to obtain high precision features that enable capture and retention of tumor spheroids in a perfusion flow stream that provides oxygen and nutrient requirements sufficient to sustain viability over several days. Use of 3D printing enables rapid design cycles, based on optimization of computational fluid dynamic analyses, much more rapidly than conventional techniques involving replica molding from photolithographic masters. Ultimately, these prototype design and fabrication approaches may be useful in generating highly multiplexed monolithic arrays capable of supporting rapid and efficient evaluation of therapeutic candidates in the cancer drug discovery process.},\n\turldate = {2022-06-01},\n\tjournal = {Frontiers in Medical Technology},\n\tauthor = {Markoski, Alex and Wong, Ian Y. and Borenstein, Jeffrey T.},\n\tmonth = apr,\n\tyear = {2021},\n\tpages = {646441},\n}\n\n\n\n Microfluidic systems for the analysis of tissue models of cancer and other diseases are rapidly emerging, with an increasing recognition that perfusion is required to recapitulate critical aspects of the in vivo microenvironment. Here we report on the first application of 3D printing for the fabrication of monolithic devices suitable for capturing and imaging tumor spheroids under dynamic perfusion flow. Resolution of the printing process has been refined to a level sufficient to obtain high precision features that enable capture and retention of tumor spheroids in a perfusion flow stream that provides oxygen and nutrient requirements sufficient to sustain viability over several days. Use of 3D printing enables rapid design cycles, based on optimization of computational fluid dynamic analyses, much more rapidly than conventional techniques involving replica molding from photolithographic masters. Ultimately, these prototype design and fabrication approaches may be useful in generating highly multiplexed monolithic arrays capable of supporting rapid and efficient evaluation of therapeutic candidates in the cancer drug discovery process.\n
\n\n\n\n \n\n \n \n \n \n \n \n Topological data analysis of collective and individual epithelial cells using persistent homology of loops.\n \n \n \n \n\n\n \n Bhaskar, D.; Zhang, W. Y.; and Wong, I. Y.\n\n\n \n\n\n\n Soft Matter, 17(17): 4653–4664. 2021.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{bhaskar_topological_2021,\n\ttitle = {Topological data analysis of collective and individual epithelial cells using persistent homology of loops},\n\tvolume = {17},\n\tissn = {1744-683X, 1744-6848},\n\turl = {http://xlink.rsc.org/?DOI=D1SM00072A},\n\tdoi = {10.1039/D1SM00072A},\n\tabstract = {Topology-based machine learning classifies complex spatial patterns of epithelial cells into distinct phases. The presence and stability of spatially-connected loops is an effective measure of topological similarity, even when population size varies significantly due to proliferation. \n , \n \n Interacting, self-propelled particles such as epithelial cells can dynamically self-organize into complex multicellular patterns, which are challenging to classify without \n a priori \n information. Classically, different phases and phase transitions have been described based on local ordering, which may not capture structural features at larger length scales. Instead, topological data analysis (TDA) determines the stability of spatial connectivity at varying length scales ( \n i.e. \n persistent homology), and can compare different particle configurations based on the “cost” of reorganizing one configuration into another. Here, we demonstrate a topology-based machine learning approach for unsupervised profiling of individual and collective phases based on large-scale loops. We show that these topological loops ( \n i.e. \n dimension 1 homology) are robust to variations in particle number and density, particularly in comparison to connected components ( \n i.e. \n dimension 0 homology). We use TDA to map out phase diagrams for simulated particles with varying adhesion and propulsion, at constant population size as well as when proliferation is permitted. Next, we use this approach to profile our recent experiments on the clustering of epithelial cells in varying growth factor conditions, which are compared to our simulations. Finally, we characterize the robustness of this approach at varying length scales, with sparse sampling, and over time. Overall, we envision TDA will be broadly applicable as a model-agnostic approach to analyze active systems with varying population size, from cytoskeletal motors to motile cells to flocking or swarming animals.},\n\tlanguage = {en},\n\tnumber = {17},\n\turldate = {2022-06-01},\n\tjournal = {Soft Matter},\n\tauthor = {Bhaskar, Dhananjay and Zhang, William Y. and Wong, Ian Y.},\n\tyear = {2021},\n\tpages = {4653--4664},\n}\n\n\n\n Topology-based machine learning classifies complex spatial patterns of epithelial cells into distinct phases. The presence and stability of spatially-connected loops is an effective measure of topological similarity, even when population size varies significantly due to proliferation. , Interacting, self-propelled particles such as epithelial cells can dynamically self-organize into complex multicellular patterns, which are challenging to classify without a priori information. Classically, different phases and phase transitions have been described based on local ordering, which may not capture structural features at larger length scales. Instead, topological data analysis (TDA) determines the stability of spatial connectivity at varying length scales ( i.e. persistent homology), and can compare different particle configurations based on the “cost” of reorganizing one configuration into another. Here, we demonstrate a topology-based machine learning approach for unsupervised profiling of individual and collective phases based on large-scale loops. We show that these topological loops ( i.e. dimension 1 homology) are robust to variations in particle number and density, particularly in comparison to connected components ( i.e. dimension 0 homology). We use TDA to map out phase diagrams for simulated particles with varying adhesion and propulsion, at constant population size as well as when proliferation is permitted. Next, we use this approach to profile our recent experiments on the clustering of epithelial cells in varying growth factor conditions, which are compared to our simulations. Finally, we characterize the robustness of this approach at varying length scales, with sparse sampling, and over time. Overall, we envision TDA will be broadly applicable as a model-agnostic approach to analyze active systems with varying population size, from cytoskeletal motors to motile cells to flocking or swarming animals.\n
\n\n\n\n
\n\n \n \n 2020\n \n \n (2)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n \n Multifunctional soft machines based on stimuli-responsive hydrogels: from freestanding hydrogels to smart integrated systems.\n \n \n \n \n\n\n \n Ding, M.; Jing, L.; Yang, H.; Machnicki, C.; Fu, X.; Li, K.; Wong, I.; and Chen, P.\n\n\n \n\n\n\n Materials Today Advances, 8: 100088. December 2020.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{ding_multifunctional_2020,\n\ttitle = {Multifunctional soft machines based on stimuli-responsive hydrogels: from freestanding hydrogels to smart integrated systems},\n\tvolume = {8},\n\tissn = {25900498},\n\tshorttitle = {Multifunctional soft machines based on stimuli-responsive hydrogels},\n\turl = {https://linkinghub.elsevier.com/retrieve/pii/S2590049820300357},\n\tdoi = {10.1016/j.mtadv.2020.100088},\n\tabstract = {Hydrogels possess exceptional physical and chemical properties that render them appealing components for soft actuators, wearable technologies, healthcare devices, and human interactive robots. Especially, the stimuli-responsive hydrogels can sense and perform smart functions in the presence of various stimuli that collectively contribute to the intelligence of the soft machine systems. Furthermore, facile modification of hydrogels with other functional groups/additives/nanofillers substantially expands their functionalities and further broadens the scope of their application. Designing suitable hydrogels with adequate capabilities and engineering effective configurations are of supreme importance for the development of advanced hydrogel-based soft machines. Herein, this review summarizes recent advances of stimuli-responsive hydrogels in multifunctional soft machines, such as robotics, actuators, and sensors. Functions including multistimuli responsiveness, self-healing, and high biocompatibility can be endowed to the soft machines through designing advanced hydrogel materials, which would not be possible with an approach based on conventional elastic materials (e.g. rubbers, elastomers). To close, future opportunities and challenges this field faces are emphasized and discussed for the development of exciting new hydrogel-based devices in real-world conditions.},\n\tlanguage = {en},\n\turldate = {2020-09-20},\n\tjournal = {Materials Today Advances},\n\tauthor = {Ding, M. and Jing, L. and Yang, H. and Machnicki, C.E. and Fu, X. and Li, K. and Wong, I.Y. and Chen, P.-Y.},\n\tmonth = dec,\n\tyear = {2020},\n\tpages = {100088},\n}\n\n\n\n Hydrogels possess exceptional physical and chemical properties that render them appealing components for soft actuators, wearable technologies, healthcare devices, and human interactive robots. Especially, the stimuli-responsive hydrogels can sense and perform smart functions in the presence of various stimuli that collectively contribute to the intelligence of the soft machine systems. Furthermore, facile modification of hydrogels with other functional groups/additives/nanofillers substantially expands their functionalities and further broadens the scope of their application. Designing suitable hydrogels with adequate capabilities and engineering effective configurations are of supreme importance for the development of advanced hydrogel-based soft machines. Herein, this review summarizes recent advances of stimuli-responsive hydrogels in multifunctional soft machines, such as robotics, actuators, and sensors. Functions including multistimuli responsiveness, self-healing, and high biocompatibility can be endowed to the soft machines through designing advanced hydrogel materials, which would not be possible with an approach based on conventional elastic materials (e.g. rubbers, elastomers). To close, future opportunities and challenges this field faces are emphasized and discussed for the development of exciting new hydrogel-based devices in real-world conditions.\n
\n\n\n\n \n\n \n \n \n \n \n Mechanophenotyping of 3D multicellular clusters using displacement arrays of rendered tractions.\n \n \n \n\n\n \n Leggett, S. E.; Patel, M.; Valentin, T. M.; Gamboa, L.; Khoo, A. S.; Williams, E. K.; Franck, C.; and Wong, I. Y.\n\n\n \n\n\n\n Proceedings of the National Academy of Sciences of the United States of America, 117(11): 5655–5663. 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{leggett_mechanophenotyping_2020,\n\ttitle = {Mechanophenotyping of {3D} multicellular clusters using displacement arrays of rendered tractions},\n\tvolume = {117},\n\tissn = {1091-6490},\n\tdoi = {10.1073/pnas.1918296117},\n\tabstract = {Epithelial tissues mechanically deform the surrounding extracellular matrix during embryonic development, wound repair, and tumor invasion. Ex vivo measurements of such multicellular tractions within three-dimensional (3D) biomaterials could elucidate collective dissemination during disease progression and enable preclinical testing of targeted antimigration therapies. However, past 3D traction measurements have been low throughput due to the challenges of imaging and analyzing information-rich 3D material deformations. Here, we demonstrate a method to profile multicellular clusters in a 96-well-plate format based on spatially heterogeneous contractile, protrusive, and circumferential tractions. As a case study, we profile multicellular clusters across varying states of the epithelial-mesenchymal transition, revealing a successive loss of protrusive and circumferential tractions, as well as the formation of localized contractile tractions with elongated cluster morphologies. These cluster phenotypes were biochemically perturbed by using drugs, biasing toward traction signatures of different epithelial or mesenchymal states. This higher-throughput analysis is promising to systematically interrogate and perturb aberrant mechanobiology, which could be utilized with human-patient samples to guide personalized therapies.},\n\tlanguage = {eng},\n\tnumber = {11},\n\tjournal = {Proceedings of the National Academy of Sciences of the United States of America},\n\tauthor = {Leggett, Susan E. and Patel, Mohak and Valentin, Thomas M. and Gamboa, Lena and Khoo, Amanda S. and Williams, Evelyn Kendall and Franck, Christian and Wong, Ian Y.},\n\tyear = {2020},\n\tpmid = {32123100},\n\tpmcid = {PMC7084145},\n\tkeywords = {3D culture, Biomechanical Phenomena, Cell Line, Cell Movement, Collagen, Drug Screening Assays, Antitumor, Epithelial Cells, Epithelial-Mesenchymal Transition, Fibroins, Humans, Hydrogels, Phenotype, Precision Medicine, Primary Cell Culture, Spheroids, Cellular, Tissue Scaffolds, cell–matrix interactions, collective migration, epithelial–mesenchymal transition},\n\tpages = {5655--5663},\n}\n\n\n Epithelial tissues mechanically deform the surrounding extracellular matrix during embryonic development, wound repair, and tumor invasion. Ex vivo measurements of such multicellular tractions within three-dimensional (3D) biomaterials could elucidate collective dissemination during disease progression and enable preclinical testing of targeted antimigration therapies. However, past 3D traction measurements have been low throughput due to the challenges of imaging and analyzing information-rich 3D material deformations. Here, we demonstrate a method to profile multicellular clusters in a 96-well-plate format based on spatially heterogeneous contractile, protrusive, and circumferential tractions. As a case study, we profile multicellular clusters across varying states of the epithelial-mesenchymal transition, revealing a successive loss of protrusive and circumferential tractions, as well as the formation of localized contractile tractions with elongated cluster morphologies. These cluster phenotypes were biochemically perturbed by using drugs, biasing toward traction signatures of different epithelial or mesenchymal states. This higher-throughput analysis is promising to systematically interrogate and perturb aberrant mechanobiology, which could be utilized with human-patient samples to guide personalized therapies.\n
\n\n\n\n
\n\n \n \n 2019\n \n \n (5)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Breast Cancer Cells Transition from Mesenchymal to Amoeboid Migration in Tunable Three-Dimensional Silk-Collagen Hydrogels.\n \n \n \n\n\n \n Khoo, A. S.; Valentin, T. M.; Leggett, S. E.; Bhaskar, D.; Bye, E. M.; Benmelech, S.; Ip, B. C.; and Wong, I. Y.\n\n\n \n\n\n\n ACS Biomaterials Science & Engineering, 5(9): 4341–4354. September 2019.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{khoo_breast_2019,\n\ttitle = {Breast {Cancer} {Cells} {Transition} from {Mesenchymal} to {Amoeboid} {Migration} in {Tunable} {Three}-{Dimensional} {Silk}-{Collagen} {Hydrogels}},\n\tvolume = {5},\n\tissn = {2373-9878},\n\tdoi = {10.1021/acsbiomaterials.9b00519},\n\tabstract = {Invading cancer cells adapt their migration phenotype in response to mechanical and biochemical cues from the extracellular matrix. For instance, mesenchymal migration is associated with strong cell-matrix adhesions and an elongated morphology, while amoeboid migration is associated with minimal cell-matrix adhesions and a rounded morphology. However, it remains challenging to elucidate the role of matrix mechan-ics and biochemistry, since these are both dependent on ECM protein concentration. Here, we demonstrate a composite silk fibroin and collagen I hydrogel where stiffness and microstructure can be systematically tuned over a wide range. Using an overlay assay geometry, we show that the invasion of metastatic breast cancer cells exhibits a biphasic dependence on silk fibroin concentration at fixed collagen I concentration, first increasing as the hydrogel stiffness increases, then decreasing as the pore size of silk fibroin decreases. Indeed, mesenchymal morphology exhibits a similar biphasic depen-dence on silk fibroin concentration, while amoeboid morphologies were favored when cell-matrix adhesions were less effective. We used exogenous biochemical treatment to perturb cells towards increased contractility and a mesenchymal morphology, as well as to disrupt cytoskeletal function and promote an amoeboid morphology. Overall, we envision that this tunable biomaterial platform in a 96-well plate format will be widely applicable to screen cancer cell migration against combinations of designer biomaterials and targeted inhibitors.},\n\tlanguage = {eng},\n\tnumber = {9},\n\tjournal = {ACS Biomaterials Science \\& Engineering},\n\tauthor = {Khoo, Amanda S. and Valentin, Thomas M. and Leggett, Susan E. and Bhaskar, Dhananjay and Bye, Elisa M. and Benmelech, Shoham and Ip, Blanche C. and Wong, Ian Y.},\n\tmonth = sep,\n\tyear = {2019},\n\tpmid = {31517039},\n\tpmcid = {PMC6739834},\n\tkeywords = {3D culture, extracellular matrix, high content screening, interpenetrating network, overlay assay},\n\tpages = {4341--4354},\n}\n\n\n\n Invading cancer cells adapt their migration phenotype in response to mechanical and biochemical cues from the extracellular matrix. For instance, mesenchymal migration is associated with strong cell-matrix adhesions and an elongated morphology, while amoeboid migration is associated with minimal cell-matrix adhesions and a rounded morphology. However, it remains challenging to elucidate the role of matrix mechan-ics and biochemistry, since these are both dependent on ECM protein concentration. Here, we demonstrate a composite silk fibroin and collagen I hydrogel where stiffness and microstructure can be systematically tuned over a wide range. Using an overlay assay geometry, we show that the invasion of metastatic breast cancer cells exhibits a biphasic dependence on silk fibroin concentration at fixed collagen I concentration, first increasing as the hydrogel stiffness increases, then decreasing as the pore size of silk fibroin decreases. Indeed, mesenchymal morphology exhibits a similar biphasic depen-dence on silk fibroin concentration, while amoeboid morphologies were favored when cell-matrix adhesions were less effective. We used exogenous biochemical treatment to perturb cells towards increased contractility and a mesenchymal morphology, as well as to disrupt cytoskeletal function and promote an amoeboid morphology. Overall, we envision that this tunable biomaterial platform in a 96-well plate format will be widely applicable to screen cancer cell migration against combinations of designer biomaterials and targeted inhibitors.\n
\n\n\n\n \n\n \n \n \n \n \n \n 3D printed self-adhesive PEGDA–PAA hydrogels as modular components for soft actuators and microfluidics.\n \n \n \n \n\n\n \n Valentin, T. M.; DuBois, E. M.; Machnicki, C. E.; Bhaskar, D.; Cui, F. R.; and Wong, I. Y.\n\n\n \n\n\n\n Polymer Chemistry, 10(16): 2015–2028. 2019.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{valentin_3d_2019,\n\ttitle = {{3D} printed self-adhesive {PEGDA}–{PAA} hydrogels as modular components for soft actuators and microfluidics},\n\tvolume = {10},\n\tissn = {1759-9954, 1759-9962},\n\turl = {http://xlink.rsc.org/?DOI=C9PY00211A},\n\tdoi = {10.1039/C9PY00211A},\n\tabstract = {Hydrogel building blocks that are stimuli-responsive and self-adhesive could be utilized as a simple “do-it-yourself” construction set for soft machines and microfluidic devices. \n , \n Hydrogel building blocks that are stimuli-responsive and self-adhesive could be utilized as a simple “do-it-yourself” construction set for soft machines and microfluidic devices. However, conventional covalently-crosslinked hydrogels are unsuitable since they are as static materials with poor interfacial adhesion. In this article, we demonstrate ion-responsive interchangeable parts based on composite hydrogels that incorporate both covalent and ionic crosslinking. We use light-directed 3D printing to covalently-crosslink poly(ethylene glycol) diacrylate in the presence of anionic poly(acrylic acid) of much higher molecular weight. The addition of trivalent cations acts to crosslink the anionic polymer chains together. Using high cation concentrations drives strong crosslinking, which can result in dramatic hydrogel contraction. Mismatched contraction of layered ion-responsive and non-ion-responsive hydrogels can control bending and twisting actuation, which is utilized for a gripping device. Alternatively, moderate cation concentrations permit strong self-adhesion between hydrogel surfaces. LEGO-like hydrogel blocks with internal channels and external mechanical connectors can be stacked into complex microfluidic device geometries including serpentine micromixers and multilevel architectures. This approach enables “plug-and-play” hydrogel parts for ionic soft machines that mimic actuation, sensing, and fluid transport in living systems.},\n\tlanguage = {en},\n\tnumber = {16},\n\turldate = {2020-09-20},\n\tjournal = {Polymer Chemistry},\n\tauthor = {Valentin, Thomas M. and DuBois, Eric M. and Machnicki, Catherine E. and Bhaskar, Dhananjay and Cui, Francis R. and Wong, Ian Y.},\n\tyear = {2019},\n\tpages = {2015--2028},\n}\n\n\n\n Hydrogel building blocks that are stimuli-responsive and self-adhesive could be utilized as a simple “do-it-yourself” construction set for soft machines and microfluidic devices. , Hydrogel building blocks that are stimuli-responsive and self-adhesive could be utilized as a simple “do-it-yourself” construction set for soft machines and microfluidic devices. However, conventional covalently-crosslinked hydrogels are unsuitable since they are as static materials with poor interfacial adhesion. In this article, we demonstrate ion-responsive interchangeable parts based on composite hydrogels that incorporate both covalent and ionic crosslinking. We use light-directed 3D printing to covalently-crosslink poly(ethylene glycol) diacrylate in the presence of anionic poly(acrylic acid) of much higher molecular weight. The addition of trivalent cations acts to crosslink the anionic polymer chains together. Using high cation concentrations drives strong crosslinking, which can result in dramatic hydrogel contraction. Mismatched contraction of layered ion-responsive and non-ion-responsive hydrogels can control bending and twisting actuation, which is utilized for a gripping device. Alternatively, moderate cation concentrations permit strong self-adhesion between hydrogel surfaces. LEGO-like hydrogel blocks with internal channels and external mechanical connectors can be stacked into complex microfluidic device geometries including serpentine micromixers and multilevel architectures. This approach enables “plug-and-play” hydrogel parts for ionic soft machines that mimic actuation, sensing, and fluid transport in living systems.\n
\n\n\n\n \n\n \n \n \n \n \n \n Alginate-graphene oxide hydrogels with enhanced ionic tunability and chemomechanical stability for light-directed 3D printing.\n \n \n \n \n\n\n \n Valentin, T. M.; Landauer, A. K.; Morales, L. C.; DuBois, E. M.; Shukla, S.; Liu, M.; Stephens Valentin, L. H.; Franck, C.; Chen, P.; and Wong, I. Y.\n\n\n \n\n\n\n Carbon, 143: 447–456. March 2019.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{valentin_alginate-graphene_2019,\n\ttitle = {Alginate-graphene oxide hydrogels with enhanced ionic tunability and chemomechanical stability for light-directed {3D} printing},\n\tvolume = {143},\n\tissn = {00086223},\n\turl = {https://linkinghub.elsevier.com/retrieve/pii/S0008622318310236},\n\tdoi = {10.1016/j.carbon.2018.11.006},\n\tlanguage = {en},\n\turldate = {2020-09-20},\n\tjournal = {Carbon},\n\tauthor = {Valentin, Thomas M. and Landauer, Alexander K. and Morales, Luke C. and DuBois, Eric M. and Shukla, Shashank and Liu, Muchun and Stephens Valentin, Lauren H. and Franck, Christian and Chen, Po-Yen and Wong, Ian Y.},\n\tmonth = mar,\n\tyear = {2019},\n\tpages = {447--456},\n}\n\n\n\n \n\n \n \n \n \n \n Motility-limited aggregation of mammary epithelial cells into fractal-like clusters.\n \n \n \n\n\n \n Leggett, S. E.; Neronha, Z. J.; Bhaskar, D.; Sim, J. Y.; Perdikari, T. M.; and Wong, I. Y.\n\n\n \n\n\n\n Proceedings of the National Academy of Sciences of the United States of America, 116(35): 17298–17306. 2019.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{leggett_motility-limited_2019,\n\ttitle = {Motility-limited aggregation of mammary epithelial cells into fractal-like clusters},\n\tvolume = {116},\n\tissn = {1091-6490},\n\tdoi = {10.1073/pnas.1905958116},\n\tabstract = {Migratory cells transition between dispersed individuals and multicellular collectives during development, wound healing, and cancer. These transitions are associated with coordinated behaviors as well as arrested motility at high cell densities, but remain poorly understood at lower cell densities. Here, we show that dispersed mammary epithelial cells organize into arrested, fractal-like clusters at low density in reduced epidermal growth factor (EGF). These clusters exhibit a branched architecture with a fractal dimension of [Formula: see text], reminiscent of diffusion-limited aggregation of nonliving colloidal particles. First, cells display diminished motility in reduced EGF, which permits irreversible adhesion upon cell-cell contact. Subsequently, leader cells emerge that guide collectively migrating strands and connect clusters into space-filling networks. Thus, this living system exhibits gelation-like arrest at low cell densities, analogous to the glass-like arrest of epithelial monolayers at high cell densities. We quantitatively capture these behaviors with a jamming-like phase diagram based on local cell density and EGF. These individual to collective transitions represent an intriguing link between living and nonliving systems, with potential relevance for epithelial morphogenesis into branched architectures.},\n\tlanguage = {eng},\n\tnumber = {35},\n\tjournal = {Proceedings of the National Academy of Sciences of the United States of America},\n\tauthor = {Leggett, Susan E. and Neronha, Zachary J. and Bhaskar, Dhananjay and Sim, Jea Yun and Perdikari, Theodora Myrto and Wong, Ian Y.},\n\tyear = {2019},\n\tpmid = {31413194},\n\tpmcid = {PMC6717304},\n\tkeywords = {Cell Communication, Cell Count, Cell Line, Cell Movement, Epidermal Growth Factor, Epithelial Cells, Female, Humans, Mammary Glands, Human, collective migration, gelation, jamming},\n\tpages = {17298--17306},\n}\n\n\n\n Migratory cells transition between dispersed individuals and multicellular collectives during development, wound healing, and cancer. These transitions are associated with coordinated behaviors as well as arrested motility at high cell densities, but remain poorly understood at lower cell densities. Here, we show that dispersed mammary epithelial cells organize into arrested, fractal-like clusters at low density in reduced epidermal growth factor (EGF). These clusters exhibit a branched architecture with a fractal dimension of [Formula: see text], reminiscent of diffusion-limited aggregation of nonliving colloidal particles. First, cells display diminished motility in reduced EGF, which permits irreversible adhesion upon cell-cell contact. Subsequently, leader cells emerge that guide collectively migrating strands and connect clusters into space-filling networks. Thus, this living system exhibits gelation-like arrest at low cell densities, analogous to the glass-like arrest of epithelial monolayers at high cell densities. We quantitatively capture these behaviors with a jamming-like phase diagram based on local cell density and EGF. These individual to collective transitions represent an intriguing link between living and nonliving systems, with potential relevance for epithelial morphogenesis into branched architectures.\n
\n\n\n\n \n\n \n \n \n \n \n Mechanochemical engineering of 2D materials for multiscale biointerfaces.\n \n \n \n\n\n \n Machnicki, C. E.; Fu, F.; Jing, L.; Chen, P.; and Wong, I. Y.\n\n\n \n\n\n\n Journal of Materials Chemistry. B, 7(41): 6293–6309. 2019.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{machnicki_mechanochemical_2019,\n\ttitle = {Mechanochemical engineering of {2D} materials for multiscale biointerfaces},\n\tvolume = {7},\n\tissn = {2050-7518},\n\tdoi = {10.1039/c9tb01006h},\n\tabstract = {Atomically thin nanomaterials represent a unique paradigm for interfacing with biological systems due to their mechanical flexibility, exceptional interfacial area, and ease of chemical functionalization. In particular, these two-dimensional (2D) materials are able to bend, curve, and fold in response to biologically-generated forces or other external stimuli. Such origami-like folding of 2D materials into wrinkled or crumpled topographies allows them to withstand large deformations by accordion-like unfolding, with implications for stretchable and shape-changing devices. Here, we review how mechanically manipulated 2D materials can interact with biological systems across a multitude of length scales. We focus on recent work where wrinkling, crumpling, or bending of 2D materials permits new chemical and material properties, with four case studies: (i) programming biomolecular reactivity and enhanced sensing, (ii) directed adhesion and encapsulation of bacteria or mammalian cells, (iii) stimuli-responsive actuators and soft robotics, and (iv) stretchable barrier technologies and wearable human-scale sensors. Finally, we consider future directions for manufacturing, materials and systems integration, as well as biocompatibility. Taken together, these 2D materials may enable new avenues for ultrasensitive molecular detection, biomaterial scaffolds, soft machines, and wearable technologies.},\n\tlanguage = {eng},\n\tnumber = {41},\n\tjournal = {Journal of Materials Chemistry. B},\n\tauthor = {Machnicki, Catherine E. and Fu, Fanfan and Jing, Lin and Chen, Po-Yen and Wong, Ian Y.},\n\tyear = {2019},\n\tpmid = {31460549},\n\tpmcid = {PMC6812607},\n\tkeywords = {Engineering, Mechanical Phenomena, Nanostructures, Pliability, Robotics, Wearable Electronic Devices},\n\tpages = {6293--6309},\n}\n\n\n\n Atomically thin nanomaterials represent a unique paradigm for interfacing with biological systems due to their mechanical flexibility, exceptional interfacial area, and ease of chemical functionalization. In particular, these two-dimensional (2D) materials are able to bend, curve, and fold in response to biologically-generated forces or other external stimuli. Such origami-like folding of 2D materials into wrinkled or crumpled topographies allows them to withstand large deformations by accordion-like unfolding, with implications for stretchable and shape-changing devices. Here, we review how mechanically manipulated 2D materials can interact with biological systems across a multitude of length scales. We focus on recent work where wrinkling, crumpling, or bending of 2D materials permits new chemical and material properties, with four case studies: (i) programming biomolecular reactivity and enhanced sensing, (ii) directed adhesion and encapsulation of bacteria or mammalian cells, (iii) stimuli-responsive actuators and soft robotics, and (iv) stretchable barrier technologies and wearable human-scale sensors. Finally, we consider future directions for manufacturing, materials and systems integration, as well as biocompatibility. Taken together, these 2D materials may enable new avenues for ultrasensitive molecular detection, biomaterial scaffolds, soft machines, and wearable technologies.\n
\n\n\n\n
\n\n \n \n 2018\n \n \n (2)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Ultrastretchable Graphene-Based Molecular Barriers for Chemical Protection, Detection, and Actuation.\n \n \n \n\n\n \n Chen, P.; Zhang, M.; Liu, M.; Wong, I. Y.; and Hurt, R. H.\n\n\n \n\n\n\n ACS Nano, 12(1): 234–244. 2018.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{chen_ultrastretchable_2018,\n\ttitle = {Ultrastretchable {Graphene}-{Based} {Molecular} {Barriers} for {Chemical} {Protection}, {Detection}, and {Actuation}},\n\tvolume = {12},\n\tissn = {1936-086X},\n\tdoi = {10.1021/acsnano.7b05961},\n\tabstract = {A wide range of technologies requires barrier films to impede molecular transport between the external environment and a desired internal microclimate. Adding stretchability to barrier films would enable the applications in packaging, textiles, and flexible devices, but classical barrier materials utilize dense, ordered molecular architectures that easily fracture under small tensile strain. Here, we show that textured graphene-based coatings can serve as ultrastretchable molecular barriers expandable to 1500\\% areal strain through programmed unfolding that mimics the elasticity of polymers. These coatings retain barrier function under large deformation and can be conformally applied to planar or curved surfaces, where they are washfast and mechanically robust to cycling. These graphene-polymer bilayer structures also function as sensors or actuators by transducing chemical stimuli into mechanical deformation and electrical resistance change through asymmetric polymer swelling. These results may enable multifunctional fabrics that integrate chemical protection, sensing, and actuation, with further applications as selective barriers, membranes, stretchable electronics, or soft robotics.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {ACS Nano},\n\tauthor = {Chen, Po-Yen and Zhang, Mengke and Liu, Muchun and Wong, Ian Y. and Hurt, Robert H.},\n\tyear = {2018},\n\tpmid = {29165991},\n\tpmcid = {PMC5780244},\n\tkeywords = {Diffusion, Elasticity, Electronics, Graphite, Humans, Membranes, Artificial, Models, Molecular, Nanostructures, Polymers, Protective Clothing, Robotics, Textiles, Wearable Electronic Devices, broad-range chemical rejection, chemomechanical actuators, chemoresistive sensors, graphene oxide membrane, ultrastretchable molecular barriers},\n\tpages = {234--244},\n}\n\n\n\n A wide range of technologies requires barrier films to impede molecular transport between the external environment and a desired internal microclimate. Adding stretchability to barrier films would enable the applications in packaging, textiles, and flexible devices, but classical barrier materials utilize dense, ordered molecular architectures that easily fracture under small tensile strain. Here, we show that textured graphene-based coatings can serve as ultrastretchable molecular barriers expandable to 1500% areal strain through programmed unfolding that mimics the elasticity of polymers. These coatings retain barrier function under large deformation and can be conformally applied to planar or curved surfaces, where they are washfast and mechanically robust to cycling. These graphene-polymer bilayer structures also function as sensors or actuators by transducing chemical stimuli into mechanical deformation and electrical resistance change through asymmetric polymer swelling. These results may enable multifunctional fabrics that integrate chemical protection, sensing, and actuation, with further applications as selective barriers, membranes, stretchable electronics, or soft robotics.\n
\n\n\n\n \n\n \n \n \n \n \n Rapid, topology-based particle tracking for high-resolution measurements of large complex 3D motion fields.\n \n \n \n\n\n \n Patel, M.; Leggett, S. E.; Landauer, A. K.; Wong, I. Y.; and Franck, C.\n\n\n \n\n\n\n Scientific Reports, 8(1): 5581. 2018.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{patel_rapid_2018,\n\ttitle = {Rapid, topology-based particle tracking for high-resolution measurements of large complex {3D} motion fields},\n\tvolume = {8},\n\tissn = {2045-2322},\n\tdoi = {10.1038/s41598-018-23488-y},\n\tabstract = {Spatiotemporal tracking of tracer particles or objects of interest can reveal localized behaviors in biological and physical systems. However, existing tracking algorithms are most effective for relatively low numbers of particles that undergo displacements smaller than their typical interparticle separation distance. Here, we demonstrate a single particle tracking algorithm to reconstruct large complex motion fields with large particle numbers, orders of magnitude larger than previously tractably resolvable, thus opening the door for attaining very high Nyquist spatial frequency motion recovery in the images. Our key innovations are feature vectors that encode nearest neighbor positions, a rigorous outlier removal scheme, and an iterative deformation warping scheme. We test this technique for its accuracy and computational efficacy using synthetically and experimentally generated 3D particle images, including non-affine deformation fields in soft materials, complex fluid flows, and cell-generated deformations. We augment this algorithm with additional particle information (e.g., color, size, or shape) to further enhance tracking accuracy for high gradient and large displacement fields. These applications demonstrate that this versatile technique can rapidly track unprecedented numbers of particles to resolve large and complex motion fields in 2D and 3D images, particularly when spatial correlations exist.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {Scientific Reports},\n\tauthor = {Patel, Mohak and Leggett, Susan E. and Landauer, Alexander K. and Wong, Ian Y. and Franck, Christian},\n\tyear = {2018},\n\tpmid = {29615650},\n\tpmcid = {PMC5882970},\n\tkeywords = {Algorithms, Hydrodynamics, Imaging, Three-Dimensional, Motion, Signal-To-Noise Ratio},\n\tpages = {5581},\n}\n\n\n\n Spatiotemporal tracking of tracer particles or objects of interest can reveal localized behaviors in biological and physical systems. However, existing tracking algorithms are most effective for relatively low numbers of particles that undergo displacements smaller than their typical interparticle separation distance. Here, we demonstrate a single particle tracking algorithm to reconstruct large complex motion fields with large particle numbers, orders of magnitude larger than previously tractably resolvable, thus opening the door for attaining very high Nyquist spatial frequency motion recovery in the images. Our key innovations are feature vectors that encode nearest neighbor positions, a rigorous outlier removal scheme, and an iterative deformation warping scheme. We test this technique for its accuracy and computational efficacy using synthetically and experimentally generated 3D particle images, including non-affine deformation fields in soft materials, complex fluid flows, and cell-generated deformations. We augment this algorithm with additional particle information (e.g., color, size, or shape) to further enhance tracking accuracy for high gradient and large displacement fields. These applications demonstrate that this versatile technique can rapidly track unprecedented numbers of particles to resolve large and complex motion fields in 2D and 3D images, particularly when spatial correlations exist.\n
\n\n\n\n
\n\n \n \n 2017\n \n \n (4)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Nanomedicine: Catching tumour cells in the zone.\n \n \n \n\n\n \n Leggett, S. E.; and Wong, I. Y.\n\n\n \n\n\n\n Nature Nanotechnology, 12(3): 191–193. 2017.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n\n@article{leggett_nanomedicine_2017,\n\ttitle = {Nanomedicine: {Catching} tumour cells in the zone},\n\tvolume = {12},\n\tissn = {1748-3395},\n\tshorttitle = {Nanomedicine},\n\tdoi = {10.1038/nnano.2016.264},\n\tlanguage = {eng},\n\tnumber = {3},\n\tjournal = {Nature Nanotechnology},\n\tauthor = {Leggett, Susan E. and Wong, Ian Y.},\n\tyear = {2017},\n\tpmid = {27870839},\n\tkeywords = {Biomarkers, Tumor, Cell Separation, Gene Expression Regulation, Neoplastic, Humans, Lab-On-A-Chip Devices, Magnetic Fields, Male, Nanomedicine, Neoplastic Cells, Circulating, Prostatic Neoplasms},\n\tpages = {191--193},\n}\n\n\n\n \n\n \n \n \n \n \n From Flatland to Spaceland: Higher Dimensional Patterning with Two-Dimensional Materials.\n \n \n \n\n\n \n Chen, P.; Liu, M.; Wang, Z.; Hurt, R. H.; and Wong, I. Y.\n\n\n \n\n\n\n Advanced Materials (Deerfield Beach, Fla.), 29(23). June 2017.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{chen_flatland_2017,\n\ttitle = {From {Flatland} to {Spaceland}: {Higher} {Dimensional} {Patterning} with {Two}-{Dimensional} {Materials}},\n\tvolume = {29},\n\tissn = {1521-4095},\n\tshorttitle = {From {Flatland} to {Spaceland}},\n\tdoi = {10.1002/adma.201605096},\n\tabstract = {The creation of three-dimensional (3D) structures from two-dimensional (2D) nanomaterial building blocks enables novel chemical, mechanical or physical functionalities that cannot be realized with planar thin films or in bulk materials. Here, we review the use of emerging 2D materials to create complex out-of-plane surface topographies and 3D material architectures. We focus on recent approaches that yield periodic textures or patterns, and present four techniques as case studies: (i) wrinkling and crumpling of planar sheets, (ii) encapsulation by crumpled nanosheet shells, (iii) origami folding and kirigami cutting to create programmed curvature, and (iv) 3D printing of 2D material suspensions. Work to date in this field has primarily used graphene and graphene oxide as the 2D building blocks, and we consider how these unconventional approaches may be extended to alternative 2D materials and their heterostructures. Taken together, these emerging patterning and texturing techniques represent an intriguing alternative to conventional materials synthesis and processing methods, and are expected to contribute to the development of new composites, stretchable electronics, energy storage devices, chemical barriers, and biomaterials.},\n\tlanguage = {eng},\n\tnumber = {23},\n\tjournal = {Advanced Materials (Deerfield Beach, Fla.)},\n\tauthor = {Chen, Po-Yen and Liu, Muchun and Wang, Zhongying and Hurt, Robert H. and Wong, Ian Y.},\n\tmonth = jun,\n\tyear = {2017},\n\tpmid = {28244157},\n\tpmcid = {PMC5549278},\n\tkeywords = {2D materials, 3D printing, hierarchical structure, mechanical deformation, origami and kirigami, self-assembly},\n}\n\n\n\n The creation of three-dimensional (3D) structures from two-dimensional (2D) nanomaterial building blocks enables novel chemical, mechanical or physical functionalities that cannot be realized with planar thin films or in bulk materials. Here, we review the use of emerging 2D materials to create complex out-of-plane surface topographies and 3D material architectures. We focus on recent approaches that yield periodic textures or patterns, and present four techniques as case studies: (i) wrinkling and crumpling of planar sheets, (ii) encapsulation by crumpled nanosheet shells, (iii) origami folding and kirigami cutting to create programmed curvature, and (iv) 3D printing of 2D material suspensions. Work to date in this field has primarily used graphene and graphene oxide as the 2D building blocks, and we consider how these unconventional approaches may be extended to alternative 2D materials and their heterostructures. Taken together, these emerging patterning and texturing techniques represent an intriguing alternative to conventional materials synthesis and processing methods, and are expected to contribute to the development of new composites, stretchable electronics, energy storage devices, chemical barriers, and biomaterials.\n
\n\n\n\n \n\n \n \n \n \n \n Multicellular tumor invasion and plasticity in biomimetic materials.\n \n \n \n\n\n \n Leggett, S. E.; Khoo, A. S.; and Wong, I. Y.\n\n\n \n\n\n\n Biomaterials Science, 5(8): 1460–1479. July 2017.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{leggett_multicellular_2017,\n\ttitle = {Multicellular tumor invasion and plasticity in biomimetic materials},\n\tvolume = {5},\n\tissn = {2047-4849},\n\tdoi = {10.1039/c7bm00272f},\n\tabstract = {Cancer cell invasion through the extracellular matrix is associated with metastatic spread and therapeutic resistance. In carcinomas, the detachment and dissemination of individual cells has been associated with an epithelial-mesenchymal transition, but tumors can also invade using collective, multicellular phenotypes. This malignant tumor progression is also associated with alignment and stiffening of the surrounding extracellular matrix. Historically, tumor invasion has been investigated using 2D monolayer culture, small animal models or patient histology. These assays have been complemented by the use of natural biomaterials such as reconstituted basement membrane and collagen I. More recently, engineered materials with well-defined physical, chemical and biomolecular properties have enabled more controlled microenvironments. In this review, we highlight recent developments in multicellular tumor invasion based on microfabricated structures or hydrogels. We emphasize the role of interfacial geometries, biomaterial stiffness, matrix remodeling, and co-culture models. Finally, we discuss future directions for the field, particularly integration with precision measurements of biomaterial properties and single cell heterogeneity, standardization and scale-up of these platforms, as well as integration with patient-derived samples.},\n\tlanguage = {eng},\n\tnumber = {8},\n\tjournal = {Biomaterials Science},\n\tauthor = {Leggett, Susan E. and Khoo, Amanda S. and Wong, Ian Y.},\n\tmonth = jul,\n\tyear = {2017},\n\tpmid = {28530743},\n\tpmcid = {PMC5531215},\n\tkeywords = {Animals, Biomimetics, Extracellular Matrix, Humans, Hydrogels, Neoplasm Invasiveness, Neoplasms, Spheroids, Cellular},\n\tpages = {1460--1479},\n}\n\n\n\n Cancer cell invasion through the extracellular matrix is associated with metastatic spread and therapeutic resistance. In carcinomas, the detachment and dissemination of individual cells has been associated with an epithelial-mesenchymal transition, but tumors can also invade using collective, multicellular phenotypes. This malignant tumor progression is also associated with alignment and stiffening of the surrounding extracellular matrix. Historically, tumor invasion has been investigated using 2D monolayer culture, small animal models or patient histology. These assays have been complemented by the use of natural biomaterials such as reconstituted basement membrane and collagen I. More recently, engineered materials with well-defined physical, chemical and biomolecular properties have enabled more controlled microenvironments. In this review, we highlight recent developments in multicellular tumor invasion based on microfabricated structures or hydrogels. We emphasize the role of interfacial geometries, biomaterial stiffness, matrix remodeling, and co-culture models. Finally, we discuss future directions for the field, particularly integration with precision measurements of biomaterial properties and single cell heterogeneity, standardization and scale-up of these platforms, as well as integration with patient-derived samples.\n
\n\n\n\n \n\n \n \n \n \n \n Stereolithographic printing of ionically-crosslinked alginate hydrogels for degradable biomaterials and microfluidics.\n \n \n \n\n\n \n Valentin, T. M.; Leggett, S. E.; Chen, P.; Sodhi, J. K.; Stephens, L. H.; McClintock, H. D.; Sim, J. Y.; and Wong, I. Y.\n\n\n \n\n\n\n Lab on a Chip, 17(20): 3474–3488. 2017.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{valentin_stereolithographic_2017,\n\ttitle = {Stereolithographic printing of ionically-crosslinked alginate hydrogels for degradable biomaterials and microfluidics},\n\tvolume = {17},\n\tissn = {1473-0189},\n\tdoi = {10.1039/c7lc00694b},\n\tabstract = {3D printed biomaterials with spatial and temporal functionality could enable interfacial manipulation of fluid flows and motile cells. However, such dynamic biomaterials are challenging to implement since they must be responsive to multiple, biocompatible stimuli. Here, we show stereolithographic printing of hydrogels using noncovalent (ionic) crosslinking, which enables reversible patterning with controlled degradation. We demonstrate this approach using sodium alginate, photoacid generators and various combinations of divalent cation salts, which can be used to tune the hydrogel degradation kinetics, pattern fidelity, and mechanical properties. This approach is first utilized to template perfusable microfluidic channels within a second encapsulating hydrogel for T-junction and gradient devices. The presence and degradation of printed alginate microstructures were further verified to have minimal toxicity on epithelial cells. Degradable alginate barriers were used to direct collective cell migration from different initial geometries, revealing differences in front speed and leader cell formation. Overall, this demonstration of light-based 3D printing using non-covalent crosslinking may enable adaptive and stimuli-responsive biomaterials, which could be utilized for bio-inspired sensing, actuation, drug delivery, and tissue engineering.},\n\tlanguage = {eng},\n\tnumber = {20},\n\tjournal = {Lab on a Chip},\n\tauthor = {Valentin, Thomas M. and Leggett, Susan E. and Chen, Po-Yen and Sodhi, Jaskiranjeet K. and Stephens, Lauren H. and McClintock, Hayley D. and Sim, Jea Yun and Wong, Ian Y.},\n\tyear = {2017},\n\tpmid = {28906525},\n\tpmcid = {PMC5636682},\n\tkeywords = {Alginates, Biocompatible Materials, Cell Line, Cell Survival, Glucuronic Acid, Hexuronic Acids, Humans, Hydrogels, Materials Testing, Microfluidic Analytical Techniques, Printing, Three-Dimensional},\n\tpages = {3474--3488},\n}\n\n\n\n 3D printed biomaterials with spatial and temporal functionality could enable interfacial manipulation of fluid flows and motile cells. However, such dynamic biomaterials are challenging to implement since they must be responsive to multiple, biocompatible stimuli. Here, we show stereolithographic printing of hydrogels using noncovalent (ionic) crosslinking, which enables reversible patterning with controlled degradation. We demonstrate this approach using sodium alginate, photoacid generators and various combinations of divalent cation salts, which can be used to tune the hydrogel degradation kinetics, pattern fidelity, and mechanical properties. This approach is first utilized to template perfusable microfluidic channels within a second encapsulating hydrogel for T-junction and gradient devices. The presence and degradation of printed alginate microstructures were further verified to have minimal toxicity on epithelial cells. Degradable alginate barriers were used to direct collective cell migration from different initial geometries, revealing differences in front speed and leader cell formation. Overall, this demonstration of light-based 3D printing using non-covalent crosslinking may enable adaptive and stimuli-responsive biomaterials, which could be utilized for bio-inspired sensing, actuation, drug delivery, and tissue engineering.\n
\n\n\n\n
\n\n \n \n 2016\n \n \n (6)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Morphological single cell profiling of the epithelial-mesenchymal transition.\n \n \n \n\n\n \n Leggett, S. E.; Sim, J. Y.; Rubins, J. E.; Neronha, Z. J.; Williams, E. K.; and Wong, I. Y.\n\n\n \n\n\n\n Integrative Biology, 8(11): 1133–1144. 2016.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{leggett_morphological_2016,\n\ttitle = {Morphological single cell profiling of the epithelial-mesenchymal transition},\n\tvolume = {8},\n\tissn = {1757-9708},\n\tdoi = {10.1039/c6ib00139d},\n\tabstract = {Single cells respond heterogeneously to biochemical treatments, which can complicate the analysis of in vitro and in vivo experiments. In particular, stressful perturbations may induce the epithelial-mesenchymal transition (EMT), a transformation through which compact, sensitive cells adopt an elongated, resistant phenotype. However, classical biochemical measurements based on population averages over large numbers cannot resolve single cell heterogeneity and plasticity. Here, we use high content imaging of single cell morphology to classify distinct phenotypic subpopulations after EMT. We first characterize a well-defined EMT induction through the master regulator Snail in mammary epithelial cells over 72 h. We find that EMT is associated with increased vimentin area as well as elongation of the nucleus and cytoplasm. These morphological features were integrated into a Gaussian mixture model that classified epithelial and mesenchymal phenotypes with {\\textgreater}92\\% accuracy. We then applied this analysis to heterogeneous populations generated from less controlled EMT-inducing stimuli, including growth factors (TGF-β1), cell density, and chemotherapeutics (Taxol). Our quantitative, single cell approach has the potential to screen large heterogeneous cell populations for many types of phenotypic variability, and may thus provide a predictive assay for the preclinical assessment of targeted therapeutics.},\n\tlanguage = {eng},\n\tnumber = {11},\n\tjournal = {Integrative Biology},\n\tauthor = {Leggett, Susan E. and Sim, Jea Yun and Rubins, Jonathan E. and Neronha, Zachary J. and Williams, Evelyn Kendall and Wong, Ian Y.},\n\tyear = {2016},\n\tpmid = {27722556},\n\tpmcid = {PMC5417362},\n\tkeywords = {Cell Line, Cell Size, Computer Simulation, Epithelial Cells, Epithelial-Mesenchymal Transition, High-Throughput Screening Assays, Humans, Mesoderm, Models, Biological, Models, Statistical, Normal Distribution},\n\tpages = {1133--1144},\n}\n\n\n\n Single cells respond heterogeneously to biochemical treatments, which can complicate the analysis of in vitro and in vivo experiments. In particular, stressful perturbations may induce the epithelial-mesenchymal transition (EMT), a transformation through which compact, sensitive cells adopt an elongated, resistant phenotype. However, classical biochemical measurements based on population averages over large numbers cannot resolve single cell heterogeneity and plasticity. Here, we use high content imaging of single cell morphology to classify distinct phenotypic subpopulations after EMT. We first characterize a well-defined EMT induction through the master regulator Snail in mammary epithelial cells over 72 h. We find that EMT is associated with increased vimentin area as well as elongation of the nucleus and cytoplasm. These morphological features were integrated into a Gaussian mixture model that classified epithelial and mesenchymal phenotypes with \\textgreater92% accuracy. We then applied this analysis to heterogeneous populations generated from less controlled EMT-inducing stimuli, including growth factors (TGF-β1), cell density, and chemotherapeutics (Taxol). Our quantitative, single cell approach has the potential to screen large heterogeneous cell populations for many types of phenotypic variability, and may thus provide a predictive assay for the preclinical assessment of targeted therapeutics.\n
\n\n\n\n \n\n \n \n \n \n \n Multiscale Graphene Topographies Programmed by Sequential Mechanical Deformation.\n \n \n \n\n\n \n Chen, P.; Sodhi, J.; Qiu, Y.; Valentin, T. M.; Steinberg, R. S.; Wang, Z.; Hurt, R. H.; and Wong, I. Y.\n\n\n \n\n\n\n Advanced Materials, 28(18): 3564–3571. 2016.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{chen_multiscale_2016,\n\ttitle = {Multiscale {Graphene} {Topographies} {Programmed} by {Sequential} {Mechanical} {Deformation}},\n\tvolume = {28},\n\tissn = {1521-4095},\n\tdoi = {10.1002/adma.201506194},\n\tabstract = {Multigenerational graphene oxide architectures can be programmed by specific sequences of mechanical deformations. Each new deformation results in a progressively larger set of features decorated by smaller preexisting patterns, indicating a structural "memory." It is shown that these multiscale architectures are superhydrophobic and display excellent functionality as electrochemical electrodes.},\n\tlanguage = {eng},\n\tnumber = {18},\n\tjournal = {Advanced Materials},\n\tauthor = {Chen, Po-Yen and Sodhi, Jaskiranjeet and Qiu, Yang and Valentin, Thomas M. and Steinberg, Ruben Spitz and Wang, Zhongying and Hurt, Robert H. and Wong, Ian Y.},\n\tyear = {2016},\n\tpmid = {26996525},\n\tkeywords = {electrochemical activity, graphene, multiscale surface architectures, sequential patterning, superhydrophobicity},\n\tpages = {3564--3571},\n}\n\n\n\n Multigenerational graphene oxide architectures can be programmed by specific sequences of mechanical deformations. Each new deformation results in a progressively larger set of features decorated by smaller preexisting patterns, indicating a structural \"memory.\" It is shown that these multiscale architectures are superhydrophobic and display excellent functionality as electrochemical electrodes.\n
\n\n\n\n \n\n \n \n \n \n \n \n Use the force.\n \n \n \n \n\n\n \n Wong, I. Y.\n\n\n \n\n\n\n Science Translational Medicine, 8(325): 325ec25–325ec25. February 2016.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{wong_use_2016,\n\ttitle = {Use the force},\n\tvolume = {8},\n\tissn = {1946-6234, 1946-6242},\n\turl = {https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaf2012},\n\tdoi = {10.1126/scitranslmed.aaf2012},\n\tlanguage = {en},\n\tnumber = {325},\n\turldate = {2020-09-20},\n\tjournal = {Science Translational Medicine},\n\tauthor = {Wong, Ian Y.},\n\tmonth = feb,\n\tyear = {2016},\n\tpages = {325ec25--325ec25},\n}\n\n\n\n \n\n \n \n \n \n \n Wrinkled, wavelength-tunable graphene-based surface topographies for directing cell alignment and morphology.\n \n \n \n\n\n \n Wang, Z.; Tonderys, D.; Leggett, S. E.; Williams, E. K.; Kiani, M. T.; Steinberg, R. S.; Qiu, Y.; Wong, I. Y.; and Hurt, R. H.\n\n\n \n\n\n\n Carbon, 97: 14–24. February 2016.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n
\n\n\n@article{wang_wrinkled_2016,\n\ttitle = {Wrinkled, wavelength-tunable graphene-based surface topographies for directing cell alignment and morphology},\n\tvolume = {97},\n\tissn = {0008-6223},\n\tdoi = {10.1016/j.carbon.2015.03.040},\n\tabstract = {Textured surfaces with periodic topographical features and long-range order are highly attractive for directing cell-material interactions. They mimic physiological environments more accurately than planar surfaces and can fundamentally alter cell alignment, shape, gene expression, and cellular assembly into superstructures or microtissues. Here we demonstrate for the first time that wrinkled graphene-based surfaces are suitable as textured cell attachment substrates, and that engineered wrinkling can dramatically alter cell alignment and morphology. The wrinkled surfaces are fabricated by graphene oxide wet deposition onto pre-stretched elastomers followed by relaxation and mild thermal treatment to stabilize the films in cell culture medium. Multilayer graphene oxide films form periodic, delaminated buckle textures whose wavelengths and amplitudes can be systematically tuned by variation in the wet deposition process. Human and murine fibroblasts attach to these textured films and remain viable, while developing pronounced alignment and elongation relative to those on planar graphene controls. Compared to lithographic patterning of nanogratings, this method has advantages in the simplicity and scalability of fabrication, as well as the opportunity to couple the use of topographic cues with the unique conductive, adsorptive, or barrier properties of graphene materials for functional biomedical devices.},\n\tlanguage = {eng},\n\tjournal = {Carbon},\n\tauthor = {Wang, Zhongying and Tonderys, Daniel and Leggett, Susan E. and Williams, Evelyn Kendall and Kiani, Mehrdad T. and Steinberg, Ruben Spitz and Qiu, Yang and Wong, Ian Y. and Hurt, Robert H.},\n\tmonth = feb,\n\tyear = {2016},\n\tpmid = {25848137},\n\tpmcid = {PMC4384125},\n\tpages = {14--24},\n}\n\n\n\n Textured surfaces with periodic topographical features and long-range order are highly attractive for directing cell-material interactions. They mimic physiological environments more accurately than planar surfaces and can fundamentally alter cell alignment, shape, gene expression, and cellular assembly into superstructures or microtissues. Here we demonstrate for the first time that wrinkled graphene-based surfaces are suitable as textured cell attachment substrates, and that engineered wrinkling can dramatically alter cell alignment and morphology. The wrinkled surfaces are fabricated by graphene oxide wet deposition onto pre-stretched elastomers followed by relaxation and mild thermal treatment to stabilize the films in cell culture medium. Multilayer graphene oxide films form periodic, delaminated buckle textures whose wavelengths and amplitudes can be systematically tuned by variation in the wet deposition process. Human and murine fibroblasts attach to these textured films and remain viable, while developing pronounced alignment and elongation relative to those on planar graphene controls. Compared to lithographic patterning of nanogratings, this method has advantages in the simplicity and scalability of fabrication, as well as the opportunity to couple the use of topographic cues with the unique conductive, adsorptive, or barrier properties of graphene materials for functional biomedical devices.\n
\n\n\n\n \n\n \n \n \n \n \n Clustering and jamming in epithelial-mesenchymal co-cultures.\n \n \n \n\n\n \n Gamboa Castro, M.; Leggett, S. E.; and Wong, I. Y.\n\n\n \n\n\n\n Soft Matter, 12(40): 8327–8337. October 2016.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{gamboa_castro_clustering_2016,\n\ttitle = {Clustering and jamming in epithelial-mesenchymal co-cultures},\n\tvolume = {12},\n\tissn = {1744-6848},\n\tdoi = {10.1039/c6sm01287f},\n\tabstract = {Collective behaviors emerge from coordinated cell-cell interactions during the morphogenesis of tissues and tumors. For instance, cells may display density-dependent phase transitions from a fluid-like "unjammed" phase to a solid-like "jammed" phase, while different cell types can "self-sort". Here, we comprehensively track single cell dynamics in mixtures of sheet-forming epithelial cells and dispersed mesenchymal cells. We find that proliferating epithelial cells nucleate multicellular clusters that coarsen at a critical density, arresting migration and strengthening spatial velocity correlations. The addition of mesenchymal cells can slow cluster formation and coarsening, resulting in more dispersed individual cells with weak spatial velocity correlations. These behaviors have analogies with a jamming-unjamming transition, where the control parameters are cell density and mesenchymal fraction. This complex interplay of proliferation, clustering and correlated migration may have physical implications for understanding epithelial-mesenchymal interactions in development and disease.},\n\tlanguage = {eng},\n\tnumber = {40},\n\tjournal = {Soft Matter},\n\tauthor = {Gamboa Castro, Marielena and Leggett, Susan E. and Wong, Ian Y.},\n\tmonth = oct,\n\tyear = {2016},\n\tpmid = {27722738},\n\tpmcid = {PMC5063081},\n\tkeywords = {Animals, Cell Communication, Cell Movement, Cells, Cultured, Coculture Techniques, Epithelial Cells, Mesenchymal Stem Cells, Rats},\n\tpages = {8327--8337},\n}\n\n\n\n Collective behaviors emerge from coordinated cell-cell interactions during the morphogenesis of tissues and tumors. For instance, cells may display density-dependent phase transitions from a fluid-like \"unjammed\" phase to a solid-like \"jammed\" phase, while different cell types can \"self-sort\". Here, we comprehensively track single cell dynamics in mixtures of sheet-forming epithelial cells and dispersed mesenchymal cells. We find that proliferating epithelial cells nucleate multicellular clusters that coarsen at a critical density, arresting migration and strengthening spatial velocity correlations. The addition of mesenchymal cells can slow cluster formation and coarsening, resulting in more dispersed individual cells with weak spatial velocity correlations. These behaviors have analogies with a jamming-unjamming transition, where the control parameters are cell density and mesenchymal fraction. This complex interplay of proliferation, clustering and correlated migration may have physical implications for understanding epithelial-mesenchymal interactions in development and disease.\n
\n\n\n\n \n\n \n \n \n \n \n Hierarchical Metal Oxide Topographies Replicated from Highly Textured Graphene Oxide by Intercalation Templating.\n \n \n \n\n\n \n Chen, P.; Liu, M.; Valentin, T. M.; Wang, Z.; Spitz Steinberg, R.; Sodhi, J.; Wong, I. Y.; and Hurt, R. H.\n\n\n \n\n\n\n ACS nano, 10(12): 10869–10879. 2016.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{chen_hierarchical_2016,\n\ttitle = {Hierarchical {Metal} {Oxide} {Topographies} {Replicated} from {Highly} {Textured} {Graphene} {Oxide} by {Intercalation} {Templating}},\n\tvolume = {10},\n\tissn = {1936-086X},\n\tdoi = {10.1021/acsnano.6b05179},\n\tabstract = {Confined assembly in the intersheet gallery spaces of two-dimensional (2D) materials is an emerging templating route for creation of ultrathin material architectures. Here, we demonstrate a general synthetic route for transcribing complex wrinkled and crumpled topographies in graphene oxide (GO) films into textured metal oxides. Intercalation of hydrated metal ions into textured GO multilayer films followed by dehydration, thermal decomposition, and air oxidation produces Zn, Al, Mn, and Cu oxide films with high-fidelity replication of the original GO textures, including "multi-generational", multiscale textures that have been recently achieved through extreme graphene compression. The textured metal oxides are shown to consist of nanosheet-like aggregates of interconnected particles, whose mobility, attachment, and sintering are guided by the 2D template. This intercalation templating approach has broad applicability for the creation of complex, textured films and provides a bridging technology that can transcribe the wide variety of textures already realized in graphene into insulating and semiconducting materials. These textured metal oxide films exhibit enhanced electrochemical and photocatalytic performance over planar films and show potential as high-activity electrodes for energy storage, catalysis, and biosensing.},\n\tlanguage = {eng},\n\tnumber = {12},\n\tjournal = {ACS nano},\n\tauthor = {Chen, Po-Yen and Liu, Muchun and Valentin, Thomas M. and Wang, Zhongying and Spitz Steinberg, Ruben and Sodhi, Jaskiranjeet and Wong, Ian Y. and Hurt, Robert H.},\n\tyear = {2016},\n\tpmid = {28024363},\n\tkeywords = {electrochemical and photocatalytic activities, graphene, hierarchical surface architectures, ion intercalation, nanoscale assembly, sacrificial templating},\n\tpages = {10869--10879},\n}\n\n\n\n Confined assembly in the intersheet gallery spaces of two-dimensional (2D) materials is an emerging templating route for creation of ultrathin material architectures. Here, we demonstrate a general synthetic route for transcribing complex wrinkled and crumpled topographies in graphene oxide (GO) films into textured metal oxides. Intercalation of hydrated metal ions into textured GO multilayer films followed by dehydration, thermal decomposition, and air oxidation produces Zn, Al, Mn, and Cu oxide films with high-fidelity replication of the original GO textures, including \"multi-generational\", multiscale textures that have been recently achieved through extreme graphene compression. The textured metal oxides are shown to consist of nanosheet-like aggregates of interconnected particles, whose mobility, attachment, and sintering are guided by the 2D template. This intercalation templating approach has broad applicability for the creation of complex, textured films and provides a bridging technology that can transcribe the wide variety of textures already realized in graphene into insulating and semiconducting materials. These textured metal oxide films exhibit enhanced electrochemical and photocatalytic performance over planar films and show potential as high-activity electrodes for energy storage, catalysis, and biosensing.\n
\n\n\n\n
\n\n \n \n 2015\n \n \n (7)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n \n Neutrophils: Harbingers of metastasis?.\n \n \n \n \n\n\n \n Wong, I. Y.\n\n\n \n\n\n\n Science Translational Medicine, 7(319): 319ec220–319ec220. December 2015.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{wong_neutrophils_2015,\n\ttitle = {Neutrophils: {Harbingers} of metastasis?},\n\tvolume = {7},\n\tissn = {1946-6234, 1946-6242},\n\tshorttitle = {Neutrophils},\n\turl = {https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aad9012},\n\tdoi = {10.1126/scitranslmed.aad9012},\n\tlanguage = {en},\n\tnumber = {319},\n\turldate = {2020-09-20},\n\tjournal = {Science Translational Medicine},\n\tauthor = {Wong, Ian Y.},\n\tmonth = dec,\n\tyear = {2015},\n\tpages = {319ec220--319ec220},\n}\n\n\n\n \n\n \n \n \n \n \n \n Singled out: Exploring epigenetics.\n \n \n \n \n\n\n \n Wong, I. Y.\n\n\n \n\n\n\n Science Translational Medicine, 7(313): 313ec195–313ec195. November 2015.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{wong_singled_2015,\n\ttitle = {Singled out: {Exploring} epigenetics},\n\tvolume = {7},\n\tissn = {1946-6234, 1946-6242},\n\tshorttitle = {Singled out},\n\turl = {https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aad5512},\n\tdoi = {10.1126/scitranslmed.aad5512},\n\tlanguage = {en},\n\tnumber = {313},\n\turldate = {2020-09-20},\n\tjournal = {Science Translational Medicine},\n\tauthor = {Wong, Ian Y.},\n\tmonth = nov,\n\tyear = {2015},\n\tpages = {313ec195--313ec195},\n}\n\n\n\n \n\n \n \n \n \n \n \n Platelet impersonation.\n \n \n \n \n\n\n \n Wong, I. Y.\n\n\n \n\n\n\n Science Translational Medicine, 7(307): 307ec169–307ec169. September 2015.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{wong_platelet_2015,\n\ttitle = {Platelet impersonation},\n\tvolume = {7},\n\tissn = {1946-6234, 1946-6242},\n\turl = {https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aad3627},\n\tdoi = {10.1126/scitranslmed.aad3627},\n\tlanguage = {en},\n\tnumber = {307},\n\turldate = {2020-09-20},\n\tjournal = {Science Translational Medicine},\n\tauthor = {Wong, Ian Y.},\n\tmonth = sep,\n\tyear = {2015},\n\tpages = {307ec169--307ec169},\n}\n\n\n\n \n\n \n \n \n \n \n \n Cells choose the path less potholed.\n \n \n \n \n\n\n \n Wong, I. Y.\n\n\n \n\n\n\n Science Translational Medicine, 7(301): 301ec144–301ec144. August 2015.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{wong_cells_2015,\n\ttitle = {Cells choose the path less potholed},\n\tvolume = {7},\n\tissn = {1946-6234, 1946-6242},\n\turl = {https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aad0232},\n\tdoi = {10.1126/scitranslmed.aad0232},\n\tlanguage = {en},\n\tnumber = {301},\n\turldate = {2020-09-20},\n\tjournal = {Science Translational Medicine},\n\tauthor = {Wong, Ian Y.},\n\tmonth = aug,\n\tyear = {2015},\n\tpages = {301ec144--301ec144},\n}\n\n\n\n \n\n \n \n \n \n \n \n Electronics, freshly squeezed.\n \n \n \n \n\n\n \n Wong, I. Y.\n\n\n \n\n\n\n Science Translational Medicine, 7(295): 295ec117–295ec117. July 2015.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{wong_electronics_2015,\n\ttitle = {Electronics, freshly squeezed},\n\tvolume = {7},\n\tissn = {1946-6234, 1946-6242},\n\turl = {https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aac8114},\n\tdoi = {10.1126/scitranslmed.aac8114},\n\tlanguage = {en},\n\tnumber = {295},\n\turldate = {2020-09-20},\n\tjournal = {Science Translational Medicine},\n\tauthor = {Wong, Ian Y.},\n\tmonth = jul,\n\tyear = {2015},\n\tpages = {295ec117--295ec117},\n}\n\n\n\n \n\n \n \n \n \n \n \n A graphene security blanket.\n \n \n \n \n\n\n \n Wong, I. Y.\n\n\n \n\n\n\n Science Translational Medicine, 7(289): 289ec89–289ec89. May 2015.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{wong_graphene_2015,\n\ttitle = {A graphene security blanket},\n\tvolume = {7},\n\tissn = {1946-6234, 1946-6242},\n\turl = {https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aac5088},\n\tdoi = {10.1126/scitranslmed.aac5088},\n\tlanguage = {en},\n\tnumber = {289},\n\turldate = {2020-09-20},\n\tjournal = {Science Translational Medicine},\n\tauthor = {Wong, Ian Y.},\n\tmonth = may,\n\tyear = {2015},\n\tpages = {289ec89--289ec89},\n}\n\n\n\n \n\n \n \n \n \n \n \n Singled out: Profiling metabolic and proteomic heterogeneity.\n \n \n \n \n\n\n \n Wong, I. Y.\n\n\n \n\n\n\n Science Translational Medicine, 7(283): 283ec64–283ec64. April 2015.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{wong_singled_2015-1,\n\ttitle = {Singled out: {Profiling} metabolic and proteomic heterogeneity},\n\tvolume = {7},\n\tissn = {1946-6234, 1946-6242},\n\tshorttitle = {Singled out},\n\turl = {https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aab2767},\n\tdoi = {10.1126/scitranslmed.aab2767},\n\tlanguage = {en},\n\tnumber = {283},\n\turldate = {2020-09-20},\n\tjournal = {Science Translational Medicine},\n\tauthor = {Wong, Ian Y.},\n\tmonth = apr,\n\tyear = {2015},\n\tpages = {283ec64--283ec64},\n}\n\n\n\n
\n\n \n \n 2014\n \n \n (1)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Collective and individual migration following the epithelial-mesenchymal transition.\n \n \n \n\n\n \n Wong, I. Y.; Javaid, S.; Wong, E. A.; Perk, S.; Haber, D. A.; Toner, M.; and Irimia, D.\n\n\n \n\n\n\n Nature Materials, 13(11): 1063–1071. November 2014.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{wong_collective_2014,\n\ttitle = {Collective and individual migration following the epithelial-mesenchymal transition},\n\tvolume = {13},\n\tissn = {1476-1122},\n\tdoi = {10.1038/nmat4062},\n\tabstract = {During cancer progression, malignant cells in the tumour invade surrounding tissues. This transformation of adherent cells to a motile phenotype has been associated with the epithelial-mesenchymal transition (EMT). Here, we show that EMT-activated cells migrate through micropillar arrays as a collectively advancing front that scatters individual cells. Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers. We modelled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity. Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration. The study of multicellular behaviours with single-cell resolution should enable further quantitative insights into heterogeneous tumour invasion.},\n\tlanguage = {eng},\n\tnumber = {11},\n\tjournal = {Nature Materials},\n\tauthor = {Wong, Ian Y. and Javaid, Sarah and Wong, Elisabeth A. and Perk, Sinem and Haber, Daniel A. and Toner, Mehmet and Irimia, Daniel},\n\tmonth = nov,\n\tyear = {2014},\n\tpmid = {25129619},\n\tpmcid = {PMC4209198},\n\tkeywords = {Cell Adhesion, Cell Line, Tumor, Cell Movement, Epithelial Cells, Epithelial-Mesenchymal Transition, Humans, Models, Biological},\n\tpages = {1063--1071},\n}\n\n\n\n During cancer progression, malignant cells in the tumour invade surrounding tissues. This transformation of adherent cells to a motile phenotype has been associated with the epithelial-mesenchymal transition (EMT). Here, we show that EMT-activated cells migrate through micropillar arrays as a collectively advancing front that scatters individual cells. Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers. We modelled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity. Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration. The study of multicellular behaviours with single-cell resolution should enable further quantitative insights into heterogeneous tumour invasion.\n
\n\n\n\n
\n\n \n \n 2013\n \n \n (2)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Nanotechnology: emerging tools for biology and medicine.\n \n \n \n\n\n \n Wong, I. Y.; Bhatia, S. N.; and Toner, M.\n\n\n \n\n\n\n Genes & Development, 27(22): 2397–2408. November 2013.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{wong_nanotechnology_2013,\n\ttitle = {Nanotechnology: emerging tools for biology and medicine},\n\tvolume = {27},\n\tissn = {1549-5477},\n\tshorttitle = {Nanotechnology},\n\tdoi = {10.1101/gad.226837.113},\n\tabstract = {Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potential to transform these paradigms by enabling exquisite structures comparable in size with biomolecules as well as unprecedented chemical and physical functionality at small length scales. Here, we review nanotechnology-based approaches for precisely measuring and perturbing living systems. Remarkably, nanotechnology can be used to characterize single molecules or cells at extraordinarily high throughput and deliver therapeutic payloads to specific locations as well as exhibit dynamic biomimetic behavior. These advances enable multimodal interfaces that may yield unexpected insights into systems biology as well as new therapeutic strategies for personalized medicine.},\n\tlanguage = {eng},\n\tnumber = {22},\n\tjournal = {Genes \\& Development},\n\tauthor = {Wong, Ian Y. and Bhatia, Sangeeta N. and Toner, Mehmet},\n\tmonth = nov,\n\tyear = {2013},\n\tpmid = {24240230},\n\tpmcid = {PMC3841729},\n\tkeywords = {Humans, Medicine, Nanoparticle, Nanotechnology, biomarker, microfluidics, microneedle, single cell, targeted delivery},\n\tpages = {2397--2408},\n}\n\n\n\n Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potential to transform these paradigms by enabling exquisite structures comparable in size with biomolecules as well as unprecedented chemical and physical functionality at small length scales. Here, we review nanotechnology-based approaches for precisely measuring and perturbing living systems. Remarkably, nanotechnology can be used to characterize single molecules or cells at extraordinarily high throughput and deliver therapeutic payloads to specific locations as well as exhibit dynamic biomimetic behavior. These advances enable multimodal interfaces that may yield unexpected insights into systems biology as well as new therapeutic strategies for personalized medicine.\n
\n\n\n\n \n\n \n \n \n \n \n Discontinuous nanoporous membranes reduce non-specific fouling for immunoaffinity cell capture.\n \n \n \n\n\n \n Mittal, S.; Wong, I. Y.; Yanik, A. A.; Deen, W. M.; and Toner, M.\n\n\n \n\n\n\n Small (Weinheim an Der Bergstrasse, Germany), 9(24): 4207–4214. December 2013.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{mittal_discontinuous_2013,\n\ttitle = {Discontinuous nanoporous membranes reduce non-specific fouling for immunoaffinity cell capture},\n\tvolume = {9},\n\tissn = {1613-6829},\n\tdoi = {10.1002/smll.201300977},\n\tabstract = {The microfluidic isolation of target cells using adhesion-based surface capture has been widely explored for biology and medicine. However, high-throughput processing can be challenging due to interfacial limitations such as transport, reaction, and non-specific fouling. Here, it is shown that antibody-functionalized capture surfaces with discontinuous permeability enable efficient target cell capture at high flow rates by decreasing fouling. Experimental characterization and theoretical modeling reveal that "wall effects" affect cell-surface interactions and promote excess surface accumulation. These issues are partially circumvented by reducing the transport and deposition of cells near the channel walls. Optimized microfluidic devices can be operated at higher cell concentrations with significant improvements in throughput.},\n\tlanguage = {eng},\n\tnumber = {24},\n\tjournal = {Small (Weinheim an Der Bergstrasse, Germany)},\n\tauthor = {Mittal, Sukant and Wong, Ian Y. and Yanik, Ahmet Ali and Deen, William M. and Toner, Mehmet},\n\tmonth = dec,\n\tyear = {2013},\n\tpmid = {23766297},\n\tkeywords = {Adsorption, Cell Line, Tumor, Equipment Design, Humans, Immunoassay, Leukocytes, Male, Microfluidic Analytical Techniques, Microfluidics, Nanopores, Nanotechnology, Particle Size, Permeability, Silicon, Surface Properties, biosensors, cell capture, microfluidics, nanoporous membranes, non-specific adsorption},\n\tpages = {4207--4214},\n}\n\n\n\n The microfluidic isolation of target cells using adhesion-based surface capture has been widely explored for biology and medicine. However, high-throughput processing can be challenging due to interfacial limitations such as transport, reaction, and non-specific fouling. Here, it is shown that antibody-functionalized capture surfaces with discontinuous permeability enable efficient target cell capture at high flow rates by decreasing fouling. Experimental characterization and theoretical modeling reveal that \"wall effects\" affect cell-surface interactions and promote excess surface accumulation. These issues are partially circumvented by reducing the transport and deposition of cells near the channel walls. Optimized microfluidic devices can be operated at higher cell concentrations with significant improvements in throughput.\n
\n\n\n\n
\n\n \n \n 2012\n \n \n (1)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Antibody-functionalized fluid-permeable surfaces for rolling cell capture at high flow rates.\n \n \n \n\n\n \n Mittal, S.; Wong, I. Y.; Deen, W. M.; and Toner, M.\n\n\n \n\n\n\n Biophysical Journal, 102(4): 721–730. February 2012.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{mittal_antibody-functionalized_2012,\n\ttitle = {Antibody-functionalized fluid-permeable surfaces for rolling cell capture at high flow rates},\n\tvolume = {102},\n\tissn = {1542-0086},\n\tdoi = {10.1016/j.bpj.2011.12.044},\n\tabstract = {Adhesion-based cell capture on surfaces in microfluidic devices forms the basis of numerous biomedical diagnostics and in vitro assays. However, the performance of these platforms is partly limited by interfacial phenomena that occur at low Reynolds numbers. In contrast, cell homing to porous vasculature is highly effective in vivo during inflammation, stem cell trafficking, and cancer metastasis. Here, we show that a porous, fluid-permeable surface functionalized with cell-specific antibodies promotes efficient and selective cell capture in vitro. This architecture is advantageous due to enhanced transport as streamlines are diverted toward the surface. Moreover, specific cell-surface interactions are promoted due to reduced shear, allowing gentle cell rolling and arrest. Together, these synergistic effects enable highly effective cell capture at flow rates more than an order of magnitude larger than those provided by existing devices with solid surfaces.},\n\tlanguage = {eng},\n\tnumber = {4},\n\tjournal = {Biophysical Journal},\n\tauthor = {Mittal, Sukant and Wong, Ian Y. and Deen, William M. and Toner, Mehmet},\n\tmonth = feb,\n\tyear = {2012},\n\tpmid = {22385842},\n\tpmcid = {PMC3283808},\n\tkeywords = {Cell Adhesion, Cell Line, Tumor, Cell Movement, Cell Separation, Humans, Immunoglobulin G, Microfluidic Analytical Techniques, Permeability, Porosity, Surface Properties, Time Factors},\n\tpages = {721--730},\n}\n\n\n\n Adhesion-based cell capture on surfaces in microfluidic devices forms the basis of numerous biomedical diagnostics and in vitro assays. However, the performance of these platforms is partly limited by interfacial phenomena that occur at low Reynolds numbers. In contrast, cell homing to porous vasculature is highly effective in vivo during inflammation, stem cell trafficking, and cancer metastasis. Here, we show that a porous, fluid-permeable surface functionalized with cell-specific antibodies promotes efficient and selective cell capture in vitro. This architecture is advantageous due to enhanced transport as streamlines are diverted toward the surface. Moreover, specific cell-surface interactions are promoted due to reduced shear, allowing gentle cell rolling and arrest. Together, these synergistic effects enable highly effective cell capture at flow rates more than an order of magnitude larger than those provided by existing devices with solid surfaces.\n
\n\n\n\n
\n\n \n \n 2011\n \n \n (1)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Subsets of human CD4(+) regulatory T cells express the peripheral homing receptor CXCR3.\n \n \n \n\n\n \n Hoerning, A.; Koss, K.; Datta, D.; Boneschansker, L.; Jones, C. N.; Wong, I. Y.; Irimia, D.; Calzadilla, K.; Benitez, F.; Hoyer, P. F.; Harmon, W. E.; and Briscoe, D. M.\n\n\n \n\n\n\n European Journal of Immunology, 41(8): 2291–2302. August 2011.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{hoerning_subsets_2011,\n\ttitle = {Subsets of human {CD4}(+) regulatory {T} cells express the peripheral homing receptor {CXCR3}},\n\tvolume = {41},\n\tissn = {1521-4141},\n\tdoi = {10.1002/eji.201041095},\n\tabstract = {Regulatory T cells (Tregs) migrate into peripheral sites of inflammation such as allografts undergoing rejection, where they serve to suppress the immune response. In this study, we find that ∼30-40\\% of human CD25(hi) FOXP3(+) CD4(+) Tregs express the peripheral CXC chemokine receptor 3 (CXCR3) and that this subset has potent immunoregulatory properties. Consistently, we observed that proliferative responses as well as IFN-γ production were significantly higher using CXCR3-depleted versus undepleted responders in the mixed lymphocyte reaction, as well as following mitogen-dependent activation of T cells. Using microfluidics, we also found that CXCR3 was functional on CXCR3(pos) Tregs, in as much as chemotaxis and directional persistence towards interferon-γ-inducible protein of 10 kDa (IP-10) was significantly greater for CXCR3(pos) than CXCR3(neg) Tregs. Following activation, CXCR3-expressing CD4(+) Tregs were maintained in vitro in cell culture in the presence of the mammalian target of rapamycin (mTOR) inhibitor rapamycin, and we detected higher numbers of circulating CXCR3(+) FOXP3(+) T cells in adult and pediatric recipients of renal transplants who were treated with mTOR-inhibitor immunosuppressive therapy. Collectively, these results demonstrate that the peripheral homing receptor CXCR3 is expressed on subset(s) of circulating human Tregs and suggest a role for CXCR3 in their recruitment into peripheral sites of inflammation.},\n\tlanguage = {eng},\n\tnumber = {8},\n\tjournal = {European Journal of Immunology},\n\tauthor = {Hoerning, André and Koss, Kerith and Datta, Dipak and Boneschansker, Leonard and Jones, Caroline N. and Wong, Ian Y. and Irimia, Daniel and Calzadilla, Katiana and Benitez, Fanny and Hoyer, Peter F. and Harmon, William E. and Briscoe, David M.},\n\tmonth = aug,\n\tyear = {2011},\n\tpmid = {21538345},\n\tpmcid = {PMC3383044},\n\tkeywords = {Adult, Cell Movement, Cell Proliferation, Cells, Cultured, Chemokine CXCL10, Child, Flow Cytometry, Forkhead Transcription Factors, Gene Expression, Humans, Immunosuppressive Agents, Interferon-gamma, Kidney Transplantation, L-Selectin, Lymphocyte Activation, Receptors, CCR4, Receptors, CXCR3, Reverse Transcriptase Polymerase Chain Reaction, Sirolimus, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory},\n\tpages = {2291--2302},\n}\n\n\n\n Regulatory T cells (Tregs) migrate into peripheral sites of inflammation such as allografts undergoing rejection, where they serve to suppress the immune response. In this study, we find that ∼30-40% of human CD25(hi) FOXP3(+) CD4(+) Tregs express the peripheral CXC chemokine receptor 3 (CXCR3) and that this subset has potent immunoregulatory properties. Consistently, we observed that proliferative responses as well as IFN-γ production were significantly higher using CXCR3-depleted versus undepleted responders in the mixed lymphocyte reaction, as well as following mitogen-dependent activation of T cells. Using microfluidics, we also found that CXCR3 was functional on CXCR3(pos) Tregs, in as much as chemotaxis and directional persistence towards interferon-γ-inducible protein of 10 kDa (IP-10) was significantly greater for CXCR3(pos) than CXCR3(neg) Tregs. Following activation, CXCR3-expressing CD4(+) Tregs were maintained in vitro in cell culture in the presence of the mammalian target of rapamycin (mTOR) inhibitor rapamycin, and we detected higher numbers of circulating CXCR3(+) FOXP3(+) T cells in adult and pediatric recipients of renal transplants who were treated with mTOR-inhibitor immunosuppressive therapy. Collectively, these results demonstrate that the peripheral homing receptor CXCR3 is expressed on subset(s) of circulating human Tregs and suggest a role for CXCR3 in their recruitment into peripheral sites of inflammation.\n
\n\n\n\n
\n\n \n \n 2010\n \n \n (4)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Directional decisions during neutrophil chemotaxis inside bifurcating channels.\n \n \n \n\n\n \n Ambravaneswaran, V.; Wong, I. Y.; Aranyosi, A. J.; Toner, M.; and Irimia, D.\n\n\n \n\n\n\n Integrative Biology, 2(11-12): 639–647. November 2010.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{ambravaneswaran_directional_2010,\n\ttitle = {Directional decisions during neutrophil chemotaxis inside bifurcating channels},\n\tvolume = {2},\n\tissn = {1757-9708},\n\tdoi = {10.1039/c0ib00011f},\n\tabstract = {The directional migration of human neutrophils in classical chemotaxis assays is often described as a "biased random walk" implying significant randomness in speed and directionality. However, these experiments are inconsistent with in vivo observations, where neutrophils can navigate effectively through complex tissue microenvironments towards their targets. Here, we demonstrate a novel biomimetic assay for neutrophil chemotaxis using enclosed microfluidic channels. Remarkably, under these enclosed conditions, neutrophils recapitulate the highly robust and efficient navigation observed in vivo. In straight channels, neutrophils undergo sustained, unidirectional motion towards a chemoattractant source. In more complex maze-like geometries, neutrophils are able to select the most direct route over 90\\% of the time. Finally, at symmetric bifurcations, neutrophils split their leading edge into two sections and a "tug of war" ensues. The competition between the two new leading edges is ultimately resolved by stochastic, symmetry-breaking behavior. This behavior is suggestive of directional decision-making localized at the leading edge and a signaling role played by the cellular cytoskeleton.},\n\tlanguage = {eng},\n\tnumber = {11-12},\n\tjournal = {Integrative Biology},\n\tauthor = {Ambravaneswaran, Vijayakrishnan and Wong, Ian Y. and Aranyosi, Alexander J. and Toner, Mehmet and Irimia, Daniel},\n\tmonth = nov,\n\tyear = {2010},\n\tpmid = {20676444},\n\tpmcid = {PMC3001269},\n\tkeywords = {Biomimetic Materials, Chemotaxis, Leukocyte, Cytoskeleton, Humans, In Vitro Techniques, Microfluidic Analytical Techniques, Models, Biological, Neutrophils, Signal Transduction, Stochastic Processes},\n\tpages = {639--647},\n}\n\n\n\n The directional migration of human neutrophils in classical chemotaxis assays is often described as a \"biased random walk\" implying significant randomness in speed and directionality. However, these experiments are inconsistent with in vivo observations, where neutrophils can navigate effectively through complex tissue microenvironments towards their targets. Here, we demonstrate a novel biomimetic assay for neutrophil chemotaxis using enclosed microfluidic channels. Remarkably, under these enclosed conditions, neutrophils recapitulate the highly robust and efficient navigation observed in vivo. In straight channels, neutrophils undergo sustained, unidirectional motion towards a chemoattractant source. In more complex maze-like geometries, neutrophils are able to select the most direct route over 90% of the time. Finally, at symmetric bifurcations, neutrophils split their leading edge into two sections and a \"tug of war\" ensues. The competition between the two new leading edges is ultimately resolved by stochastic, symmetry-breaking behavior. This behavior is suggestive of directional decision-making localized at the leading edge and a signaling role played by the cellular cytoskeleton.\n
\n\n\n\n \n\n \n \n \n \n \n \n Dynamic actuation using nano-bio interfaces.\n \n \n \n \n\n\n \n Wong, I. Y.; Almquist, B. D.; and Melosh, N. A.\n\n\n \n\n\n\n Materials Today, 13(6): 14–22. June 2010.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{wong_dynamic_2010,\n\ttitle = {Dynamic actuation using nano-bio interfaces},\n\tvolume = {13},\n\tissn = {13697021},\n\turl = {https://linkinghub.elsevier.com/retrieve/pii/S136970211070105X},\n\tdoi = {10.1016/S1369-7021(10)70105-X},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2020-09-20},\n\tjournal = {Materials Today},\n\tauthor = {Wong, Ian Y. and Almquist, Benjamin D. and Melosh, Nicholas A.},\n\tmonth = jun,\n\tyear = {2010},\n\tpages = {14--22},\n}\n\n\n\n \n\n \n \n \n \n \n Continuum model of mechanical interactions between biological cells and artificial nanostructures.\n \n \n \n\n\n \n Verma, P.; Wong, I. Y.; and Melosh, N. A.\n\n\n \n\n\n\n Biointerphases, 5(2): 37–44. June 2010.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{verma_continuum_2010,\n\ttitle = {Continuum model of mechanical interactions between biological cells and artificial nanostructures},\n\tvolume = {5},\n\tissn = {1559-4106},\n\tdoi = {10.1116/1.3431960},\n\tabstract = {The controlled insertion of artificial nanostructures into biological cells has been utilized for patch clamping, targeted drug delivery, cell lysing, and cell mechanics measurements. In this work, an elastic continuum model is implemented to treat the deformation of spherical cells in solution due to their interaction with cylindrical probes. At small deformations, the force varies nonlinearly with indentation due to global deformation of the cell shape. However, at large indentations, the force varies linearly with indentation due to more localized deformations. These trends are consistent with experimental measurements under comparable conditions and can be used to develop design rules for optimizing probe-cell interactions.},\n\tlanguage = {eng},\n\tnumber = {2},\n\tjournal = {Biointerphases},\n\tauthor = {Verma, Piyush and Wong, Ian Y. and Melosh, Nicholas A.},\n\tmonth = jun,\n\tyear = {2010},\n\tpmid = {20831347},\n\tkeywords = {Biomechanical Phenomena, Cell Physiological Phenomena, Elasticity, Models, Biological, Nanostructures, Stress, Mechanical},\n\tpages = {37--44},\n}\n\n\n\n The controlled insertion of artificial nanostructures into biological cells has been utilized for patch clamping, targeted drug delivery, cell lysing, and cell mechanics measurements. In this work, an elastic continuum model is implemented to treat the deformation of spherical cells in solution due to their interaction with cylindrical probes. At small deformations, the force varies nonlinearly with indentation due to global deformation of the cell shape. However, at large indentations, the force varies linearly with indentation due to more localized deformations. These trends are consistent with experimental measurements under comparable conditions and can be used to develop design rules for optimizing probe-cell interactions.\n
\n\n\n\n \n\n \n \n \n \n \n An electrostatic model for DNA surface hybridization.\n \n \n \n\n\n \n Wong, I. Y.; and Melosh, N. A.\n\n\n \n\n\n\n Biophysical Journal, 98(12): 2954–2963. June 2010.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{wong_electrostatic_2010,\n\ttitle = {An electrostatic model for {DNA} surface hybridization},\n\tvolume = {98},\n\tissn = {1542-0086},\n\tdoi = {10.1016/j.bpj.2010.03.017},\n\tabstract = {DNA hybridization at surfaces is a crucial process for biomolecular detection, genotyping, and gene expression analysis. However, hybridization density and kinetics can be strongly inhibited by electric fields from the negatively charged DNA as the reaction proceeds. Here, we develop an electrostatic model to optimize hybridization density and kinetics as a function of DNA surface density, salt concentrations, and applied voltages. The electrostatic repulsion from a DNA surface layer is calculated numerically and incorporated into a modified Langmuir scheme, allowing kinetic suppression of hybridization. At the low DNA probe densities typically used in assays ({\\textless}10(13)/cm(2)), electrostatics effects are largely screened and hybridization is completed with fast kinetics. However, higher hybridization densities can be achieved at intermediate DNA surface densities, albeit with slower kinetics. The application of positive voltages circumvents issues resulting from the very high DNA probe density, allowing highly enhanced hybridization densities and accelerated kinetics, and validating recent experimental measurements.},\n\tlanguage = {eng},\n\tnumber = {12},\n\tjournal = {Biophysical Journal},\n\tauthor = {Wong, Ian Y. and Melosh, Nicholas A.},\n\tmonth = jun,\n\tyear = {2010},\n\tpmid = {20550908},\n\tpmcid = {PMC2884251},\n\tkeywords = {DNA, Models, Molecular, Nucleic Acid Conformation, Nucleic Acid Hybridization, Reproducibility of Results, Salts, Static Electricity, Surface Properties},\n\tpages = {2954--2963},\n}\n\n\n\n DNA hybridization at surfaces is a crucial process for biomolecular detection, genotyping, and gene expression analysis. However, hybridization density and kinetics can be strongly inhibited by electric fields from the negatively charged DNA as the reaction proceeds. Here, we develop an electrostatic model to optimize hybridization density and kinetics as a function of DNA surface density, salt concentrations, and applied voltages. The electrostatic repulsion from a DNA surface layer is calculated numerically and incorporated into a modified Langmuir scheme, allowing kinetic suppression of hybridization. At the low DNA probe densities typically used in assays (\\textless10(13)/cm(2)), electrostatics effects are largely screened and hybridization is completed with fast kinetics. However, higher hybridization densities can be achieved at intermediate DNA surface densities, albeit with slower kinetics. The application of positive voltages circumvents issues resulting from the very high DNA probe density, allowing highly enhanced hybridization densities and accelerated kinetics, and validating recent experimental measurements.\n
\n\n\n\n
\n\n \n \n 2009\n \n \n (1)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Directed hybridization and melting of DNA linkers using counterion-screened electric fields.\n \n \n \n\n\n \n Wong, I. Y.; and Melosh, N. A.\n\n\n \n\n\n\n Nano Letters, 9(10): 3521–3526. October 2009.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{wong_directed_2009,\n\ttitle = {Directed hybridization and melting of {DNA} linkers using counterion-screened electric fields},\n\tvolume = {9},\n\tissn = {1530-6992},\n\tdoi = {10.1021/nl901710n},\n\tabstract = {Dynamic self-assembly using responsive, "smart" materials such as DNA is a promising route toward reversible assembly and patterning of nanostructures for error-corrected fabrication, enhanced biosensors, drug delivery and gene therapy. DNA linkers were designed with strategically placed mismatches, allowing rapid attachment and release from a surface in a counterion-screened electric field. These electrostatic fields are inherently highly localized, directing assembly with nanometer precision while avoiding harmful electrochemical reactions. We show that depending on the sign of the applied field, the DNA hybridization density is strongly enhanced or diminished due to the high negative charge density of immobilized DNA. This use of dynamic fields rather than static templates enables fabrication of heterogeneously hybridized electrodes with different functional moieties, despite the use of identical linker sequences.},\n\tlanguage = {eng},\n\tnumber = {10},\n\tjournal = {Nano Letters},\n\tauthor = {Wong, Ian Y. and Melosh, Nicholas A.},\n\tmonth = oct,\n\tyear = {2009},\n\tpmid = {19606816},\n\tkeywords = {Base Sequence, DNA, Electric Conductivity, Freezing, Molecular Sequence Data, Nucleic Acid Hybridization},\n\tpages = {3521--3526},\n}\n\n\n\n Dynamic self-assembly using responsive, \"smart\" materials such as DNA is a promising route toward reversible assembly and patterning of nanostructures for error-corrected fabrication, enhanced biosensors, drug delivery and gene therapy. DNA linkers were designed with strategically placed mismatches, allowing rapid attachment and release from a surface in a counterion-screened electric field. These electrostatic fields are inherently highly localized, directing assembly with nanometer precision while avoiding harmful electrochemical reactions. We show that depending on the sign of the applied field, the DNA hybridization density is strongly enhanced or diminished due to the high negative charge density of immobilized DNA. This use of dynamic fields rather than static templates enables fabrication of heterogeneously hybridized electrodes with different functional moieties, despite the use of identical linker sequences.\n
\n\n\n\n
\n\n \n \n 2008\n \n \n (1)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Electronically activated actin protein polymerization and alignment.\n \n \n \n\n\n \n Wong, I. Y.; Footer, M. J.; and Melosh, N. A.\n\n\n \n\n\n\n Journal of the American Chemical Society, 130(25): 7908–7915. June 2008.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{wong_electronically_2008,\n\ttitle = {Electronically activated actin protein polymerization and alignment},\n\tvolume = {130},\n\tissn = {1520-5126},\n\tdoi = {10.1021/ja7103284},\n\tabstract = {Biological systems are the paragon of dynamic self-assembly, using a combination of spatially localized protein complexation, ion concentration, and protein modification to coordinate a diverse set of self-assembling components. Biomimetic materials based upon biologically inspired design principles or biological components have had some success at replicating these traits, but have difficulty capturing the dynamic aspects and diversity of biological self-assembly. Here, we demonstrate that the polymerization of ion-sensitive proteins can be dynamically regulated using electronically enhanced ion mixing and monomer concentration. Initially, the global activity of the cytoskeletal protein actin is inhibited using a low-ionic strength buffer that minimizes ion complexation and protein-protein interactions. Nucleation and growth of actin filaments are then triggered by a low-frequency AC voltage, which causes local enhancement of the actin monomer concentration and mixing with Mg(2+). The location and extent of polymerization are governed by the voltage and frequency, producing highly ordered structures unprecedented in bulk experiments. Polymerization rate and filament orientation could be independently controlled using a combination of low-frequency (approximately 100 Hz) and high frequency (1 MHz) AC voltages, creating a range of macromolecular architectures from network hydrogel microparticles to highly aligned arrays of actin filaments with approximately 750 nm periodicity. Since a wide range of proteins are activated upon complexation with charged species, this approach may be generally applicable to a variety of biopolymers and proteins.},\n\tlanguage = {eng},\n\tnumber = {25},\n\tjournal = {Journal of the American Chemical Society},\n\tauthor = {Wong, Ian Y. and Footer, Matthew J. and Melosh, Nicholas A.},\n\tmonth = jun,\n\tyear = {2008},\n\tpmid = {18507467},\n\tkeywords = {Actins, Electrodes, Electromagnetic Fields, Electrons, Kinetics, Polymers, Protein Structure, Quaternary},\n\tpages = {7908--7915},\n}\n\n\n\n Biological systems are the paragon of dynamic self-assembly, using a combination of spatially localized protein complexation, ion concentration, and protein modification to coordinate a diverse set of self-assembling components. Biomimetic materials based upon biologically inspired design principles or biological components have had some success at replicating these traits, but have difficulty capturing the dynamic aspects and diversity of biological self-assembly. Here, we demonstrate that the polymerization of ion-sensitive proteins can be dynamically regulated using electronically enhanced ion mixing and monomer concentration. Initially, the global activity of the cytoskeletal protein actin is inhibited using a low-ionic strength buffer that minimizes ion complexation and protein-protein interactions. Nucleation and growth of actin filaments are then triggered by a low-frequency AC voltage, which causes local enhancement of the actin monomer concentration and mixing with Mg(2+). The location and extent of polymerization are governed by the voltage and frequency, producing highly ordered structures unprecedented in bulk experiments. Polymerization rate and filament orientation could be independently controlled using a combination of low-frequency (approximately 100 Hz) and high frequency (1 MHz) AC voltages, creating a range of macromolecular architectures from network hydrogel microparticles to highly aligned arrays of actin filaments with approximately 750 nm periodicity. Since a wide range of proteins are activated upon complexation with charged species, this approach may be generally applicable to a variety of biopolymers and proteins.\n
\n\n\n\n
\n\n \n \n 2007\n \n \n (1)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n \n Dynamic control of biomolecular activity using electrical interfaces.\n \n \n \n \n\n\n \n Wong, I. Y.; Footer, M. J.; and Melosh, N. A.\n\n\n \n\n\n\n Soft Matter, 3(3): 267–274. 2007.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n \n
Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n\n@article{wong_dynamic_2007,\n\ttitle = {Dynamic control of biomolecular activity using electrical interfaces},\n\tvolume = {3},\n\tissn = {1744-683X, 1744-6848},\n\turl = {http://xlink.rsc.org/?DOI=B607279H},\n\tdoi = {10.1039/B607279H},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2020-09-20},\n\tjournal = {Soft Matter},\n\tauthor = {Wong, Ian Y. and Footer, Matthew J. and Melosh, Nicholas A.},\n\tyear = {2007},\n\tpages = {267--274},\n}\n\n\n\n
\n\n \n \n 2006\n \n \n (1)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Microscopic structure and elasticity of weakly aggregated colloidal gels.\n \n \n \n\n\n \n Dinsmore, A. D.; Prasad, V.; Wong, I. Y.; and Weitz, D. A.\n\n\n \n\n\n\n Physical Review Letters, 96(18): 185502. May 2006.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n
\n\n\n@article{dinsmore_microscopic_2006,\n\ttitle = {Microscopic structure and elasticity of weakly aggregated colloidal gels},\n\tvolume = {96},\n\tissn = {0031-9007},\n\tdoi = {10.1103/PhysRevLett.96.185502},\n\tabstract = {We directly probe the microscopic structure, connectivity, and elasticity of colloidal gels using confocal microscopy. We show that the gel is a random network of one-dimensional chains of particles. By measuring thermal fluctuations, we determine the effective spring constant between pairs of particles as a function of separation; this is in agreement with the theory for fractal chains. Long-range attractions between particles lead to freely rotating bonds, and the gel is stabilized by multiple connections among the chains. By contrast, short-range attractions lead to bonds that resist bending, with dramatically suppressed formation of loops of particles.},\n\tlanguage = {eng},\n\tnumber = {18},\n\tjournal = {Physical Review Letters},\n\tauthor = {Dinsmore, A. D. and Prasad, V. and Wong, I. Y. and Weitz, D. A.},\n\tmonth = may,\n\tyear = {2006},\n\tpmid = {16712371},\n\tpages = {185502},\n}\n\n\n\n We directly probe the microscopic structure, connectivity, and elasticity of colloidal gels using confocal microscopy. We show that the gel is a random network of one-dimensional chains of particles. By measuring thermal fluctuations, we determine the effective spring constant between pairs of particles as a function of separation; this is in agreement with the theory for fractal chains. Long-range attractions between particles lead to freely rotating bonds, and the gel is stabilized by multiple connections among the chains. By contrast, short-range attractions lead to bonds that resist bending, with dramatically suppressed formation of loops of particles.\n
\n\n\n\n
\n\n\n\n\n \n \n 2004\n \n \n (1)\n \n \n
\n \n \n \n
\n \n \n\n \n \n \n \n \n Anomalous diffusion probes microstructure dynamics of entangled F-actin networks.\n \n \n \n\n\n \n Wong, I. Y.; Gardel, M. L.; Reichman, D. R.; Weeks, E. R.; Valentine, M. T.; Bausch, A. R.; and Weitz, D. A.\n\n\n \n\n\n\n Physical Review Letters, 92(17): 178101. April 2004.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n\n\n\n\n\n \n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
\n\n\n@article{wong_anomalous_2004,\n\ttitle = {Anomalous diffusion probes microstructure dynamics of entangled {F}-actin networks},\n\tvolume = {92},\n\tissn = {0031-9007},\n\tdoi = {10.1103/PhysRevLett.92.178101},\n\tabstract = {We study the thermal motion of colloidal tracer particles in entangled actin filament (F-actin) networks, where the particle radius is comparable to the mesh size of the F-actin network. In this regime, the ensemble-averaged mean-squared displacement of the particles is proportional to tau(gamma), where 0{\\textless}gamma{\\textless}1 from 0.1{\\textless}tau{\\textless}100 s and depends only on the ratio of the probe radius to mesh size. By directly imaging hundreds of particles over 20 min, we determine this anomalous subdiffusion is due to the dynamics of infrequent and large jumps particles make between distinct pores in the network.},\n\tlanguage = {eng},\n\tnumber = {17},\n\tjournal = {Physical Review Letters},\n\tauthor = {Wong, I. Y. and Gardel, M. L. and Reichman, D. R. and Weeks, Eric R. and Valentine, M. T. and Bausch, A. R. and Weitz, D. A.},\n\tmonth = apr,\n\tyear = {2004},\n\tpmid = {15169197},\n\tkeywords = {Actins, Colloids, Cytoskeleton, Diffusion, Particle Size, Thermodynamics},\n\tpages = {178101},\n}\n\n\n\n We study the thermal motion of colloidal tracer particles in entangled actin filament (F-actin) networks, where the particle radius is comparable to the mesh size of the F-actin network. In this regime, the ensemble-averaged mean-squared displacement of the particles is proportional to tau(gamma), where 0\\textlessgamma\\textless1 from 0.1\\textlesstau\\textless100 s and depends only on the ratio of the probe radius to mesh size. By directly imaging hundreds of particles over 20 min, we determine this anomalous subdiffusion is due to the dynamics of infrequent and large jumps particles make between distinct pores in the network.\n
\n\n\n