Analysis of toxic amyloid fibril interactions at natively derived membranes by ellipsometry

LEONENKO, Zoya, SMITH, Rachel A. S., NABOK, Aleksey, BLAKEMAN, Ben J. F., XUE, Wei-Feng, ABELL, Benjamin and SMITH, David P. (2015). Analysis of toxic amyloid fibril interactions at natively derived membranes by ellipsometry. PLOS ONE, 10 (7), e0132309.

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Official URL: http://journals.plos.org/plosone/article?id=10.137...
Link to published version:: 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
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Identification Number: 10.1371/journal.pone.0132309
Depositing User: Marguerite Lyons
Date Deposited: 13 Aug 2015 11:06
Last Modified: 19 Oct 2016 22:55
URI: http://shura.shu.ac.uk/id/eprint/10781

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