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?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

Goodchild, Sophia C, Sheynis, Tania, Thompson, Rebecca, Tipping, Kevin W, Xue, Wei-Feng, Ranson, Neil A, Beales, Paul A, Hewitt, Eric W, Radford, Sheena E (2014) ?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH. PLoS ONE, 9 (8). Article Number 104492. ISSN 1932-6203. (doi:10.1371/journal.pone.0104492) (KAR id:42155)


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 ?2-microglobulin (?2m), 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 ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m 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 fibril-induced membrane damage. We show that ?2m 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 ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA.

Item Type: Article
DOI/Identification number: 10.1371/journal.pone.0104492
Subjects: Q Science > QC Physics
Q Science > QD Chemistry
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Wei-Feng Xue
Date Deposited: 08 Aug 2014 14:56 UTC
Last Modified: 25 Sep 2020 13:42 UTC
Resource URI: (The current URI for this page, for reference purposes)

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