Soluble protofibrils as metastable intermediates in simulations of amyloid fibril degradation induced by lipid vesicles

TitleSoluble protofibrils as metastable intermediates in simulations of amyloid fibril degradation induced by lipid vesicles
Publication TypeJournal Article
Year of Publication2010
AuthorsFriedman R., Pellarin R., Caflisch A.
JournalThe Journal of Physical Chemistry Letters
Volume1
Issue2
Pagination471-474
Date PublishedJan 21 2010
Type of ArticleResearch Article
KeywordsAlzheimer’s disease, coarse-grained, membrane, molecular dynamics, phenomenological models
Abstract

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.

URLhttp://dx.doi.org/10.1021/jz900318t
DOI10.1021/jz900318t
pubindex

0124

Alternate JournalJ. Phys. Chem. Lett.
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