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U.S.A."],"published-print":{"date-parts":[[2022,8,2]]},"abstract":"<jats:p>Primary nucleation is the fundamental event that initiates the conversion of proteins from their normal physiological forms into pathological amyloid aggregates associated with the onset and development of disorders including systemic amyloidosis, as well as the neurodegenerative conditions Alzheimer\u2019s and Parkinson\u2019s diseases. It has become apparent that the presence of surfaces can dramatically modulate nucleation. However, the underlying physicochemical parameters governing this process have been challenging to elucidate, with interfaces in some cases having been found to accelerate aggregation, while in others they can inhibit the kinetics of this process. Here we show through kinetic analysis that for three different fibril-forming proteins, interfaces affect the aggregation reaction mainly through modulating the primary nucleation step. Moreover, we show through direct measurements of the Gibbs free energy of adsorption, combined with theory and coarse-grained computer simulations, that overall nucleation rates are suppressed at high and at low surface interaction strengths but significantly enhanced at intermediate strengths, and we verify these regimes experimentally. Taken together, these results provide a quantitative description of the fundamental process which triggers amyloid formation and shed light on the key factors that control this process.<\/jats:p>","DOI":"10.1073\/pnas.2109718119","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T14:17:59Z","timestamp":1659017879000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":44,"title":["Adsorption free energy predicts amyloid protein nucleation rates"],"prefix":"10.1073","volume":"119","author":[{"given":"Zenon","family":"Toprakcioglu","sequence":"first","affiliation":[{"name":"Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Kamada","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6931-5041","authenticated-orcid":false,"given":"Thomas C. 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