Goodchild, SC, Sheynis, T, Thompson, R et al. (6 more authors) (2014) β-microglobulin amyloid fibril-induced membrane disruption is enhanced by endosomal lipids and acidic pH. PLoS ONE, 9 (8). e104492. ISSN 1932-6203
Abstract
Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of β-microglobulin (βm), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which βm-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of βm monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibrilinduced membrane damage. We show that βm fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between βm fibrils and membranes of endosomal origin may play a role in the molecular mechanism of βm amyloid-associated osteoarticular tissue destruction in DRA.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2014, Goodchild, SC, Sheynis, T, Thompson, R, Tipping, KW, Xue, WF, Ranson, NA, Beales, PA, Hewitt, EW and Radford, SE. This is an Open Access article distributed in accordance with the Creative Commons Attribution (CC BY 4.0) licence, which permits others to distribute, remix, adapt, build upon this work, and license their derivative works on different terms, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 22 Sep 2014 10:52 |
Last Modified: | 22 Oct 2015 23:03 |
Published Version: | http://dx.doi.org/10.1371/journal.pone.0104492 |
Status: | Published |
Publisher: | Public Library of Science |
Identification Number: | 10.1371/journal.pone.0104492 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:80196 |