Document Type

Post-Print

Publication Date

5-2020

Abstract

The membrane binding behaviors of beta-amyloid fibrils, dimers to pentamers, from solution to lipid raft surfaces, were investigated using coarse-grained (CG) MD simulations. Our CG rafts contain phospholipid, cholesterol (with or without tail- or headgroup modifications), and with or without asymmetrically distributed monosialotetrahexosylganglioside (GM1). All rafts exhibited liquid-ordered (Lo), liquid-disordered (Ld), and interfacial Lo/Ld (Lod) domains, with domain sizes depending on cholesterol structure. For rafts without GM1, all fibrils bound to the Lod domains. Specifically, dimer fibrils bound exclusively via the C-terminal, while larger fibrils could bind via other protein regions. Interestingly, a membrane-inserted state was detected for a trimer fibril in a raft with tail-group modified cholesterol. For rafts containing GM1, fibrils bound either to the GM1-clusters, with numerous membrane-bound conformations, or to the non-GM1-containing-Lod domains via the C-terminal. Our results indicate beta-amyloid fibrils bind to Lod domains or GM1, with diversified membrane-bound conformations, in structurally heterogeneous lipid membranes.

Identifier

PMID: 32179374

DOI

10.1016/j.bpc.2020.106355

Publisher

Elsevier B.V.

ISSN

03014622

Publication Information

Biophysical Chemistry

Included in

Physics Commons

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