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Self-consistent analytical solutions to the kinetics of lipid-induced protein aggregation.

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Titel: Self-consistent analytical solutions to the kinetics of lipid-induced protein aggregation.
Autoren: Stevenson, Alisdair1,2 thomas.michaels@bc.biol.ethz.ch, Voderholzer, David1, Michaels, Thomas C. T.1,2
Quelle: Journal of Chemical Physics. 10/14/2025, Vol. 163 Issue 14, p1-15. 15p.
Schlagwörter: *SELF-consistent field theory, *AMYLOID beta-protein, *NEURODEGENERATION, *BILAYER lipid membranes, *NUCLEATION
Abstract: The aggregation of proteins into amyloid fibrils is a hallmark of several neurodegenerative disorders, including Parkinson's disease. A growing body of experimental evidence highlights the significant role lipid membranes play in modulating this aggregation process, particularly for proteins such as α-synuclein. Despite this, there has been a lack of quantitative theoretical frameworks capable of describing the kinetics of lipid-induced protein aggregation. In this work, we develop an analytical theoretical model that explicitly incorporates lipid-mediated interactions into the aggregation kinetics. By formulating rate equations in terms of lipid surface coverage and applying a fixed-point analysis, we derive self-consistent solutions for the full timecourse of aggregation. Our model captures both one-step and two-step nucleation mechanisms and enables the prediction of key kinetic observables, including half-times and maximal growth rates. These results provide a quantitative foundation for interpreting experimental data and offer new mechanistic insights into how lipids influence the self-assembly of amyloidogenic proteins. [ABSTRACT FROM AUTHOR]
Datenbank: Academic Search Index
Beschreibung
Abstract:The aggregation of proteins into amyloid fibrils is a hallmark of several neurodegenerative disorders, including Parkinson's disease. A growing body of experimental evidence highlights the significant role lipid membranes play in modulating this aggregation process, particularly for proteins such as α-synuclein. Despite this, there has been a lack of quantitative theoretical frameworks capable of describing the kinetics of lipid-induced protein aggregation. In this work, we develop an analytical theoretical model that explicitly incorporates lipid-mediated interactions into the aggregation kinetics. By formulating rate equations in terms of lipid surface coverage and applying a fixed-point analysis, we derive self-consistent solutions for the full timecourse of aggregation. Our model captures both one-step and two-step nucleation mechanisms and enables the prediction of key kinetic observables, including half-times and maximal growth rates. These results provide a quantitative foundation for interpreting experimental data and offer new mechanistic insights into how lipids influence the self-assembly of amyloidogenic proteins. [ABSTRACT FROM AUTHOR]
ISSN:00219606
DOI:10.1063/5.0279601