Amyloid aggregation on lipid bilayers and its impact on membrane permeability

TitleAmyloid aggregation on lipid bilayers and its impact on membrane permeability
Publication TypeJournal Article
Year of Publication2009
AuthorsFriedman R., Pellarin R., Caflisch A.
JournalJ. Mol. Biol.
Volume387
Issue2
Pagination407-415
Date Published2009 Mar 27
Type of ArticleResearch Article
ISSN1089-8638
KeywordsAmyloid, Computer Simulation, Kinetics, Lipid Bilayers, Models, Biological, Peptides, Permeability, Protein Structure, Quaternary, Time Factors, Unilamellar Liposomes
Abstract

Fibrillar protein aggregates (amyloids) are involved in several common pathologies, e.g., Alzheimer's disease and type II diabetes. Accumulating evidence suggests that toxicity in amyloid-related diseases originates from the deposition of protein aggregates on the cell membrane, which results in bilayer disruption and cell leakage. The molecular mechanism of damage to the membrane, however, is still obscure. To shed light on it we have performed coarse-grained molecular dynamics simulations of fibril-forming amphipathic peptides in the presence of lipid vesicles. The simulation results show that highly amyloidogenic peptides fibrillate on the surface of the vesicle, damaging the bilayer and promoting leakage. In contrast, the ordered aggregation of peptides with low amyloidogenicity is hindered by the vesicles. Remarkably, leakage from the vesicle is caused by growing aggregates, but not mature fibrils. The simulation results provide a basis for understanding the range of aggregation behavior that is observed in experiments with fibril-forming (poly)peptides.

DOI10.1016/j.jmb.2008.12.036
pubindex

0109

Alternate JournalJ. Mol. Biol.
PubMed ID19133272
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