Comparative analysis of the relative fragmentation stabilities of polymorphic alpha-synuclein amyloid fibrils

SANAMI, Sarina, PURTON, Tracey J., SMITH, David P., TUITE, Mick F. and XUE, Wei-Feng (2022). Comparative analysis of the relative fragmentation stabilities of polymorphic alpha-synuclein amyloid fibrils. Biomolecules, 12 (5): 630.

[img]
Preview
PDF
biomolecules-12-00630.pdf - Published Version
Creative Commons Attribution.

Download (2MB) | Preview
[img]
Preview
PDF (Supplementary table)
biomolecules-1639177-supplementary.pdf - Supplemental Material
Creative Commons Attribution.

Download (119kB) | Preview
Official URL: https://www.mdpi.com/2218-273X/12/5/630
Open Access URL: https://www.mdpi.com/2218-273X/12/5/630/pdf?versio... (Published version)
Link to published version:: https://doi.org/10.3390/biom12050630
Related URLs:

    Abstract

    The division of amyloid fibril particles through fragmentation is implicated in the progression of human neurodegenerative disorders such as Parkinson’s disease. Fragmentation of amyloid fibrils plays a crucial role in the propagation of the amyloid state encoded in their three-dimensional structures and may have an important role in the spreading of potentially pathological properties and phenotypes in amyloid-associated diseases. However, despite the mechanistic importance of fibril fragmentation, the relative stabilities of different types or different polymorphs of amyloid fibrils toward fragmentation remain to be quantified. We have previously developed an approach to compare the relative stabilities of different types of amyloid fibrils toward fragmentation. In this study, we show that controlled sonication, a widely used method of mechanical perturbation for amyloid seed generation, can be used as a form of mechanical perturbation for rapid comparative assessment of the relative fragmentation stabilities of different amyloid fibril structures. This approach is applied to assess the relative fragmentation stabilities of amyloid formed in vitro from wild type (WT) α-synuclein and two familial mutant variants of α-synuclein (A30P and A53T) that generate morphologically different fibril structures. Our results demonstrate that the fibril fragmentation stabilities of these different α-synuclein fibril polymorphs are all highly length dependent but distinct, with both A30P and A53T α-synuclein fibrils displaying increased resistance towards sonication-induced fibril fragmentation compared with WT α-synuclein fibrils. These conclusions show that fragmentation stabilities of different amyloid fibril polymorph structures can be diverse and suggest that the approach we report here will be useful in comparing the relative stabilities of amyloid fibril types or fibril polymorphs toward fragmentation under different biological conditions.

    Item Type: Article
    Additional Information: ** From MDPI via Jisc Publications Router ** Licence for this article: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 2218-273X **History: published 25-04-2022; accepted 14-04-2022
    Uncontrolled Keywords: atomic force microscopy, amyloid, fibril fragmentation, fibril division, stability, image analysis, sonication
    Identification Number: https://doi.org/10.3390/biom12050630
    SWORD Depositor: Colin Knott
    Depositing User: Colin Knott
    Date Deposited: 27 Apr 2022 09:39
    Last Modified: 09 May 2022 10:44
    URI: https://shura.shu.ac.uk/id/eprint/30158

    Actions (login required)

    View Item View Item

    Downloads

    Downloads per month over past year

    View more statistics