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R. Friedman; R. Pellarin; A. Caflisch

Journal: J. Phys. Chem. Lett.
Year: 2010
Volume: 1
Issue: 2
Pages: 471-474
DOI: 10.1021/jz900318t
Type of Publication: Journal Article

Alzheimer’s disease; coarse-grained; membrane; molecular dynamics; phenomenological models


Amyloid fibril disaggregation has been observed recently upon incubation with lipid vesicles, challenging the view of fibrils as end states of the aggregation process in vivo. Here, we follow fibril disaggregation in the presence of lipid vesicles by means of molecular dynamics simulations, using simplified models of peptides and lipids. The simulation results show that disaggregation is driven by an entropy increase and yields soluble protofibrillar intermediates. These intermediates are different from the metastable oligomers observed during fibril formation, and their stability depends on the morphology of the parent fibril.