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The Division of Amyloid Fibrils: Systematic Comparison of Fibril Fragmentation Stability by Linking Theory with Experiments.

Beal, David M., Tournus, Magali, Marchante, Ricardo, Purton, Tracey J., Smith, David P., Tuite, Mick F., Doumic, Marie, Xue, Wei-Feng (2020) The Division of Amyloid Fibrils: Systematic Comparison of Fibril Fragmentation Stability by Linking Theory with Experiments. iScience, 23 (9). Article Number 101512. E-ISSN 2589-0042. (doi:10.1016/j.isci.2020.101512) (KAR id:85700)

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https://doi.org/10.1016/j.isci.2020.101512

Abstract

The division of amyloid protein fibrils is required for the propagation of the amyloid state and is an important contributor to their stability, pathogenicity, and normal function. Here, we combine kinetic nanoscale imaging experiments with analysis of a mathematical model to resolve and compare the division stability of amyloid fibrils. Our theoretical results show that the division of any type of filament results in self-similar length distributions distinct to each fibril type and the conditions applied. By applying these theoretical results to profile the dynamical stability toward breakage for four different amyloid types, we reveal particular differences in the division properties of disease-related amyloid formed from α-synuclein when compared with non-disease associated model amyloid, the former showing lowered intrinsic stability toward breakage and increased likelihood of shedding smaller particles. Our results enable the comparison of protein filaments' intrinsic dynamic stabilities, which are key to unraveling their toxic and infectious potentials.

Item Type: Article
DOI/Identification number: 10.1016/j.isci.2020.101512
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Wei-Feng Xue
Date Deposited: 27 Jan 2021 15:00 UTC
Last Modified: 29 Jan 2021 04:13 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/85700 (The current URI for this page, for reference purposes)
Beal, David M.: https://orcid.org/0000-0002-1819-315X
Tuite, Mick F.: https://orcid.org/0000-0002-5214-540X
Xue, Wei-Feng: https://orcid.org/0000-0002-6504-0404
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