Mapping surface hydrophobicity of $α$-synuclein oligomers at the nanoscale. Lee, J., Sang, J. C, Rodrigues, M., Carr, A. R, Horrocks, M. H, De, S., Bongiovanni, M. N, Flagmeier, P., Dobson, C. M, Wales, D. J, Lee, S. F, & Klenerman, D. Nano Lett., 18(12):7494–7501, American Chemical Society (ACS), December, 2018. abstract bibtex Proteins fold into a single structural ensemble but can also misfold into many diverse structures including small aggregates and fibrils, which differ in their toxicity. The aggregate surface properties play an important role in how they interact with the plasma membrane and cellular organelles, potentially inducing cellular toxicity, however, these properties have not been measured to date due to the lack of suitable methods. Here, we used a spectrally resolved, super-resolution imaging method combined with an environmentally sensitive fluorescent dye to measure the surface hydrophobicity of individual aggregates formed by the protein $α$-synuclein ($α$S), whose aggregation is associated with Parkinson's disease. We show that the surface of soluble oligomers is more hydrophobic than fibrils and populates a diverse range of coexisting states. Overall, our data show that the conversion of oligomers to fibril-like aggregates and ultimately to fibrils results in a reduction in both hydrophobicity and the variation in hydrophobicity. This funneling characteristic of the energy landscape explains many of the observed properties of $α$S aggregates and may be a common feature of aggregating proteins.
@ARTICLE{Lee2018-ep,
title = "Mapping surface hydrophobicity of $\alpha$-synuclein oligomers
at the nanoscale",
author = "Lee, Ji-Eun and Sang, Jason C and Rodrigues, Margarida and Carr,
Alexander R and Horrocks, Mathew H and De, Suman and
Bongiovanni, Marie N and Flagmeier, Patrick and Dobson,
Christopher M and Wales, David J and Lee, Steven F and
Klenerman, David",
abstract = "Proteins fold into a single structural ensemble but can also
misfold into many diverse structures including small aggregates
and fibrils, which differ in their toxicity. The aggregate
surface properties play an important role in how they interact
with the plasma membrane and cellular organelles, potentially
inducing cellular toxicity, however, these properties have not
been measured to date due to the lack of suitable methods. Here,
we used a spectrally resolved, super-resolution imaging method
combined with an environmentally sensitive fluorescent dye to
measure the surface hydrophobicity of individual aggregates
formed by the protein $\alpha$-synuclein ($\alpha$S), whose
aggregation is associated with Parkinson's disease. We show that
the surface of soluble oligomers is more hydrophobic than
fibrils and populates a diverse range of coexisting states.
Overall, our data show that the conversion of oligomers to
fibril-like aggregates and ultimately to fibrils results in a
reduction in both hydrophobicity and the variation in
hydrophobicity. This funneling characteristic of the energy
landscape explains many of the observed properties of $\alpha$S
aggregates and may be a common feature of aggregating proteins.",
journal = "Nano Lett.",
publisher = "American Chemical Society (ACS)",
volume = 18,
number = 12,
pages = "7494--7501",
month = dec,
year = 2018,
keywords = "Nile red; Super-resolution spectroscopy; alpha-synuclein;
hydrophobicity; protein aggregation; spectral imaging",
copyright = "http://pubs.acs.org/page/policy/authorchoice\_ccby\_termsofuse.html",
language = "en"
}
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F","Klenerman, D."],"bibdata":{"bibtype":"article","type":"article","title":"Mapping surface hydrophobicity of $α$-synuclein oligomers at the nanoscale","author":[{"propositions":[],"lastnames":["Lee"],"firstnames":["Ji-Eun"],"suffixes":[]},{"propositions":[],"lastnames":["Sang"],"firstnames":["Jason","C"],"suffixes":[]},{"propositions":[],"lastnames":["Rodrigues"],"firstnames":["Margarida"],"suffixes":[]},{"propositions":[],"lastnames":["Carr"],"firstnames":["Alexander","R"],"suffixes":[]},{"propositions":[],"lastnames":["Horrocks"],"firstnames":["Mathew","H"],"suffixes":[]},{"propositions":[],"lastnames":["De"],"firstnames":["Suman"],"suffixes":[]},{"propositions":[],"lastnames":["Bongiovanni"],"firstnames":["Marie","N"],"suffixes":[]},{"propositions":[],"lastnames":["Flagmeier"],"firstnames":["Patrick"],"suffixes":[]},{"propositions":[],"lastnames":["Dobson"],"firstnames":["Christopher","M"],"suffixes":[]},{"propositions":[],"lastnames":["Wales"],"firstnames":["David","J"],"suffixes":[]},{"propositions":[],"lastnames":["Lee"],"firstnames":["Steven","F"],"suffixes":[]},{"propositions":[],"lastnames":["Klenerman"],"firstnames":["David"],"suffixes":[]}],"abstract":"Proteins fold into a single structural ensemble but can also misfold into many diverse structures including small aggregates and fibrils, which differ in their toxicity. The aggregate surface properties play an important role in how they interact with the plasma membrane and cellular organelles, potentially inducing cellular toxicity, however, these properties have not been measured to date due to the lack of suitable methods. Here, we used a spectrally resolved, super-resolution imaging method combined with an environmentally sensitive fluorescent dye to measure the surface hydrophobicity of individual aggregates formed by the protein $α$-synuclein ($α$S), whose aggregation is associated with Parkinson's disease. We show that the surface of soluble oligomers is more hydrophobic than fibrils and populates a diverse range of coexisting states. Overall, our data show that the conversion of oligomers to fibril-like aggregates and ultimately to fibrils results in a reduction in both hydrophobicity and the variation in hydrophobicity. This funneling characteristic of the energy landscape explains many of the observed properties of $α$S aggregates and may be a common feature of aggregating proteins.","journal":"Nano Lett.","publisher":"American Chemical Society (ACS)","volume":"18","number":"12","pages":"7494–7501","month":"December","year":"2018","keywords":"Nile red; Super-resolution spectroscopy; alpha-synuclein; hydrophobicity; protein aggregation; spectral imaging","copyright":"http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html","language":"en","bibtex":"@ARTICLE{Lee2018-ep,\n title = \"Mapping surface hydrophobicity of $\\alpha$-synuclein oligomers\n at the nanoscale\",\n author = \"Lee, Ji-Eun and Sang, Jason C and Rodrigues, Margarida and Carr,\n Alexander R and Horrocks, Mathew H and De, Suman and\n Bongiovanni, Marie N and Flagmeier, Patrick and Dobson,\n Christopher M and Wales, David J and Lee, Steven F and\n Klenerman, David\",\n abstract = \"Proteins fold into a single structural ensemble but can also\n misfold into many diverse structures including small aggregates\n and fibrils, which differ in their toxicity. The aggregate\n surface properties play an important role in how they interact\n with the plasma membrane and cellular organelles, potentially\n inducing cellular toxicity, however, these properties have not\n been measured to date due to the lack of suitable methods. Here,\n we used a spectrally resolved, super-resolution imaging method\n combined with an environmentally sensitive fluorescent dye to\n measure the surface hydrophobicity of individual aggregates\n formed by the protein $\\alpha$-synuclein ($\\alpha$S), whose\n aggregation is associated with Parkinson's disease. We show that\n the surface of soluble oligomers is more hydrophobic than\n fibrils and populates a diverse range of coexisting states.\n Overall, our data show that the conversion of oligomers to\n fibril-like aggregates and ultimately to fibrils results in a\n reduction in both hydrophobicity and the variation in\n hydrophobicity. This funneling characteristic of the energy\n landscape explains many of the observed properties of $\\alpha$S\n aggregates and may be a common feature of aggregating proteins.\",\n journal = \"Nano Lett.\",\n publisher = \"American Chemical Society (ACS)\",\n volume = 18,\n number = 12,\n pages = \"7494--7501\",\n month = dec,\n year = 2018,\n keywords = \"Nile red; Super-resolution spectroscopy; alpha-synuclein;\n hydrophobicity; protein aggregation; spectral imaging\",\n copyright = \"http://pubs.acs.org/page/policy/authorchoice\\_ccby\\_termsofuse.html\",\n language = \"en\"\n}\n\n","author_short":["Lee, J.","Sang, J. C","Rodrigues, M.","Carr, A. R","Horrocks, M. H","De, S.","Bongiovanni, M. N","Flagmeier, P.","Dobson, C. M","Wales, D. J","Lee, S. 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