Fibril Fragmentation Enhances Amyloid Cytotoxicity

Xue, Wei-Feng and Hellewell, Andrew L. and Gosal, Walraj S. and Homans, Steve W. and Hewitt, Eric W. and Radford, Sheena E. (2009) Fibril Fragmentation Enhances Amyloid Cytotoxicity. Journal of Biological Chemistry, 284 (49). pp. 34272-34282. ISSN 0021-9258. (doi:https://doi.org/10.1074/jbc.M109.049809) (Full text available)

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http://dx.doi.org/10.1074/jbc.M109.049809

Abstract

Fibrils associated with amyloid disease are molecular assemblies of key biological importance, yet how cells respond to the presence of amyloid remains unclear. Cellular responses may not only depend on the chemical composition or molecular properties of the amyloid fibrils, but their physical attributes such as length, width, or surface area may also play important roles. Here, we report a systematic investigation of the effect of fragmentation on the structural and biological properties of amyloid fibrils. In addition to the expected relationship between fragmentation and the ability to seed, we show a striking finding that fibril length correlates with the ability to disrupt membranes and to reduce cell viability. Thus, despite otherwise unchanged molecular architecture, shorter fibrillar samples show enhanced cytotoxic potential than their longer counterparts. The results highlight the importance of fibril length in amyloid disease, with fragmentation not only providing a mechanism by which fibril load can be rapidly increased but also creating fibrillar species of different dimensions that can endow new or enhanced biological properties such as amyloid cytotoxicity.

Item Type: Article
Subjects: Q Science
Q Science > QC Physics
Q Science > QD Chemistry
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Wei-Feng Xue
Date Deposited: 09 Oct 2012 13:16 UTC
Last Modified: 07 Aug 2018 09:33 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/31442 (The current URI for this page, for reference purposes)
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