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:: https://doi.org/10.1371/journal.pone.0132309
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    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 - Does NOT include content added after October 2018: Biomolecular Sciences Research Centre
    Identification Number: https://doi.org/10.1371/journal.pone.0132309
    Page Range: e0132309
    Depositing User: Users 3084 not found.
    Date Deposited: 13 Aug 2015 11:06
    Last Modified: 09 Oct 2018 09:00
    URI: http://shura.shu.ac.uk/id/eprint/10781

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