@article{RN165,
   author = {Ivey, J. W. and Latouche, E. L. and Richards, M. L. and Lesser, G. J. and Debinski, W. and Davalos, R. V. and Verbridge, S. S.},
   title = {Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant},
   journal = {Biophys J},
   volume = {113},
   number = {2},
   pages = {472-480},
   note = {1542-0086
Ivey, Jill W
Latouche, Eduardo L
Richards, Megan L
Lesser, Glenn J
Debinski, Waldemar
Davalos, Rafael V
Verbridge, Scott S
P30 CA012197/CA/NCI NIH HHS/United States
R01 CA213423/CA/NCI NIH HHS/United States
R21 CA192042/CA/NCI NIH HHS/United States
Journal Article
United States
2017/07/27
Biophys J. 2017 Jul 25;113(2):472-480. doi: 10.1016/j.bpj.2017.06.014.},
   abstract = {Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 μs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 μs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application.},
   keywords = {Animals
Astrocytes/drug effects/pathology
Biomechanical Phenomena
Cell Death/drug effects
Cell Line, Tumor
Cell Size
Coculture Techniques
Collagen
Electromagnetic Fields
Electroporation/*methods
Ephrin-A1/*pharmacology
Finite Element Analysis
Glioma/drug therapy/pathology/therapy
Humans
Hydrogels
Membrane Potentials
Models, Biological
Molecular Targeted Therapy/*methods
Rats
Receptor, EphA2/metabolism},
   ISSN = {0006-3495 (Print)
0006-3495},
   DOI = {10.1016/j.bpj.2017.06.014},
   year = {2017},
   type = {Journal Article}
}

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S."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Ivey"],"firstnames":["J.","W."],"suffixes":[]},{"propositions":[],"lastnames":["Latouche"],"firstnames":["E.","L."],"suffixes":[]},{"propositions":[],"lastnames":["Richards"],"firstnames":["M.","L."],"suffixes":[]},{"propositions":[],"lastnames":["Lesser"],"firstnames":["G.","J."],"suffixes":[]},{"propositions":[],"lastnames":["Debinski"],"firstnames":["W."],"suffixes":[]},{"propositions":[],"lastnames":["Davalos"],"firstnames":["R.","V."],"suffixes":[]},{"propositions":[],"lastnames":["Verbridge"],"firstnames":["S.","S."],"suffixes":[]}],"title":"Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant","journal":"Biophys J","volume":"113","number":"2","pages":"472-480","note":"1542-0086 Ivey, Jill W Latouche, Eduardo L Richards, Megan L Lesser, Glenn J Debinski, Waldemar Davalos, Rafael V Verbridge, Scott S P30 CA012197/CA/NCI NIH HHS/United States R01 CA213423/CA/NCI NIH HHS/United States R21 CA192042/CA/NCI NIH HHS/United States Journal Article United States 2017/07/27 Biophys J. 2017 Jul 25;113(2):472-480. doi: 10.1016/j.bpj.2017.06.014.","abstract":"Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 μs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 μs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application.","keywords":"Animals Astrocytes/drug effects/pathology Biomechanical Phenomena Cell Death/drug effects Cell Line, Tumor Cell Size Coculture Techniques Collagen Electromagnetic Fields Electroporation/*methods Ephrin-A1/*pharmacology Finite Element Analysis Glioma/drug therapy/pathology/therapy Humans Hydrogels Membrane Potentials Models, Biological Molecular Targeted Therapy/*methods Rats Receptor, EphA2/metabolism","issn":"0006-3495 (Print) 0006-3495","doi":"10.1016/j.bpj.2017.06.014","year":"2017","bibtex":"@article{RN165,\n author = {Ivey, J. W. and Latouche, E. L. and Richards, M. L. and Lesser, G. J. and Debinski, W. and Davalos, R. V. and Verbridge, S. S.},\n title = {Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant},\n journal = {Biophys J},\n volume = {113},\n number = {2},\n pages = {472-480},\n note = {1542-0086\nIvey, Jill W\nLatouche, Eduardo L\nRichards, Megan L\nLesser, Glenn J\nDebinski, Waldemar\nDavalos, Rafael V\nVerbridge, Scott S\nP30 CA012197/CA/NCI NIH HHS/United States\nR01 CA213423/CA/NCI NIH HHS/United States\nR21 CA192042/CA/NCI NIH HHS/United States\nJournal Article\nUnited States\n2017/07/27\nBiophys J. 2017 Jul 25;113(2):472-480. doi: 10.1016/j.bpj.2017.06.014.},\n abstract = {Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 μs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 μs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application.},\n keywords = {Animals\nAstrocytes/drug effects/pathology\nBiomechanical Phenomena\nCell Death/drug effects\nCell Line, Tumor\nCell Size\nCoculture Techniques\nCollagen\nElectromagnetic Fields\nElectroporation/*methods\nEphrin-A1/*pharmacology\nFinite Element Analysis\nGlioma/drug therapy/pathology/therapy\nHumans\nHydrogels\nMembrane Potentials\nModels, Biological\nMolecular Targeted Therapy/*methods\nRats\nReceptor, EphA2/metabolism},\n ISSN = {0006-3495 (Print)\n0006-3495},\n DOI = {10.1016/j.bpj.2017.06.014},\n year = {2017},\n type = {Journal Article}\n}\n\n","author_short":["Ivey, J. W.","Latouche, E. L.","Richards, M. L.","Lesser, G. J.","Debinski, W.","Davalos, R. V.","Verbridge, S. S."],"key":"RN165","id":"RN165","bibbaseid":"ivey-latouche-richards-lesser-debinski-davalos-verbridge-enhancingirreversibleelectroporationbymanipulatingcellularbiophysicswithamolecularadjuvant-2017","role":"author","urls":{},"keyword":["Animals Astrocytes/drug effects/pathology Biomechanical Phenomena Cell Death/drug effects Cell Line","Tumor Cell Size Coculture Techniques Collagen Electromagnetic Fields Electroporation/*methods Ephrin-A1/*pharmacology Finite Element Analysis Glioma/drug therapy/pathology/therapy Humans Hydrogels Membrane Potentials Models","Biological Molecular Targeted Therapy/*methods Rats Receptor","EphA2/metabolism"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/network/files/bdNBTZRXTsoHCgpbh","dataSources":["D4zENc4BfFNBwSYYJ","ZPLjameRikygaiM9B","3XfNmZkLe6o8CvECW","fJQsxtBoqymHQG6tL","LzxgEApraxMPkLTMn","Z2THpXfLYEJf3CB8p"],"keywords":["animals astrocytes/drug effects/pathology biomechanical phenomena cell death/drug effects cell line","tumor cell size coculture techniques collagen electromagnetic fields electroporation/*methods ephrin-a1/*pharmacology finite element analysis glioma/drug therapy/pathology/therapy humans hydrogels membrane potentials models","biological molecular targeted therapy/*methods rats receptor","epha2/metabolism"],"search_terms":["enhancing","irreversible","electroporation","manipulating","cellular","biophysics","molecular","adjuvant","ivey","latouche","richards","lesser","debinski","davalos","verbridge"],"title":"Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant","year":2017}