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Quantification of amyloid fibril polymorphism by nano-morphometry reveals the individuality of filament assembly

Aubrey, Liam D., Blakeman, Ben J. F., Lutter, Liisa, Serpell, Christopher J., Tuite, Mick F., Serpell, Louise C., Xue, Wei-Feng (2020) Quantification of amyloid fibril polymorphism by nano-morphometry reveals the individuality of filament assembly. Communications Chemistry, 3 (1). Article Number 125. ISSN 2399-3669. (doi:10.1038/s42004-020-00372-3) (KAR id:83286)

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https://doi.org/10.1038/s42004-020-00372-3

Abstract

Amyloid fibrils are highly polymorphic structures formed by many different proteins. They provide biological function but also abnormally accumulate in numerous human diseases. The physicochemical principles of amyloid polymorphism are not understood due to lack of structural insights at the single-fibril level. To identify and classify different fibril polymorphs and to quantify the level of heterogeneity is essential to decipher the precise links between amyloid structures and their functional and disease associated properties such as toxicity, strains, propagation and spreading. Employing gentle, force-distance curve-based AFM, we produce detailed images, from which the 3D reconstruction of individual filaments in heterogeneous amyloid samples is achieved. Distinctive fibril polymorphs are then classified by hierarchical clustering, and sample heterogeneity is objectively quantified. These data demonstrate the polymorphic nature of fibril populations, provide important information regarding the energy landscape of amyloid self-assembly, and offer quantitative insights into the structural basis of polymorphism in amyloid populations.

Item Type: Article
DOI/Identification number: 10.1038/s42004-020-00372-3
Uncontrolled keywords: Atomic force microscopy, Imaging techniques, Molecular self-assembly, Supramolecular polymers
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Divisions > Division of Natural Sciences > Physics and Astronomy
Depositing User: Christopher Serpell
Date Deposited: 06 Oct 2020 12:38 UTC
Last Modified: 16 Feb 2021 14:15 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/83286 (The current URI for this page, for reference purposes)
Serpell, Christopher J.: https://orcid.org/0000-0002-2848-9077
Tuite, Mick F.: https://orcid.org/0000-0002-5214-540X
Xue, Wei-Feng: https://orcid.org/0000-0002-6504-0404
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