β2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

• DOI: 10.1371/journal.pone.0104492
• Publication Date: 2014-08-06T17:54:44Z
• Authors: Sophia C. Goodchild; Tania Sheynis; Rebecca Thompson; Kevin W. Tipping; Wei-Feng Xue; Neil A. Ranson; Paul A. Beales; Eric W. Hewitt; Sheena E. Radford
• Keywords: Amyloid (mycology)

Although the molecular mechanisms underlying pathology of amyloidoses are not well understood, interaction between amyloid proteins and cell membranes is thought to play a role in several diseases. Amyloid fibrils β2-microglobulin (β2m), associated with dialysis-related amyloidosis (DRA), have been shown cause disruption anionic lipid bilayers vitro. However, effect composition chemical environment which β2m-lipid interactions occur investigated previously. Here we examine membrane damage resulting from β2m monomers bilayers. Using dye release, tryptophan fluorescence quenching confocal microscopy assays investigate pH on susceptibility liposomes fibril-induced damage. We show that modulated by enhanced acidic pH. Most strikingly, greatest degree observed for containing bis(monoacylglycero)phosphate (BMP) at pH, conditions likely reflect those encountered endocytic pathway. The results suggest endosomal origin may mechanism amyloid-associated osteoarticular tissue destruction DRA.