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Inherent variability in the kinetics of amyloid fibril formation

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SDBW03 - Advances in numerical and analytic approaches for the study of non-spatial stochastic dynamical systems in molecular biology

Co-authors: Juraj Szavits-Nossan, Kym Eden, Ryan Morris, Martin Evans and Cait MacPhee

In small volumes, the kinetics of filamentous protein self-assembly is expected to show significant variability, arising from intrinsic molecular noise. We introduce a simple stochastic model including nucleation and autocatalytic growth via elongation and fragmentation, which allows us to predict the effects of molecular noise on the kinetics of autocatalytic self-assembly. We derive an analytic expression for the lag-time distribution, which agrees well with experimental results for the fibrillation of bovine insulin. Our analysis shows that significant lag-time variability can arise from both primary nucleation and from autocatalytic growth and should provide a way to extract mechanistic information on early-stage aggregation from small-volume experiments.

This talk is part of the Isaac Newton Institute Seminar Series series.

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