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Analysis of Toxic Amyloid Fibril Interactions at Natively Derived Membranes by Ellipsometry.

Smith, Rachel A. S., Abell, Benjamin, Smith, David P., Nabok, Aleksey, Blakeman, Ben J. F., Xue, Wei-Feng (2015) Analysis of Toxic Amyloid Fibril Interactions at Natively Derived Membranes by Ellipsometry. PLOS ONE, 10 (7). e0132309. ISSN 1932-6203. (doi:10.1371/journal.pone.0132309) (KAR id:50470)

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http://doi.org/10.1371/journal.pone.0132309

Abstract

There is an ongoing debate regarding the culprits of cytotoxicity associated with amyloid disorders. Although small pre-fibrillar amyloid oligomers have been implicated as the primary toxic species, the fibrillar amyloid material itself can also induce cytotoxicity. To investigate membrane disruption and cytotoxic effects associated with intact and fragmented fibrils, the novel in situ spectroscopic technique of Total Internal Reflection Ellipsometry (TIRE) was used. Fibril lipid interactions were monitored using natively derived whole cell membranes as a model of the in vivo environment. We show that fragmented fibrils have an increased ability to disrupt these natively derived membranes by causing a loss of material from the deposited surface when compared with unfragmented fibrils. This effect was corroborated by observations of membrane disruption in live cells, and by dye release assay using synthetic liposomes. Through these studies we demonstrate the use of TIRE for the analysis of protein-lipid interactions on natively derived lipid surfaces, and provide an explanation on how amyloid fibrils can cause a toxic gain of function, while entangled amyloid plaques exert minimal biological activity.

Item Type: Article
DOI/Identification number: 10.1371/journal.pone.0132309
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Wei-Feng Xue
Date Deposited: 11 Sep 2015 09:30 UTC
Last Modified: 01 Aug 2019 10:39 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/50470 (The current URI for this page, for reference purposes)
Xue, Wei-Feng: https://orcid.org/0000-0002-6504-0404
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