Physical mechanisms of amyloid nucleation on fluid membranes.

ABSTRACT: Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein-membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways-protein-rich and lipid-rich-and quantify how the membrane fluidity and protein-membrane affinity control the relative importance of those molecular pathways. We find that the membrane's susceptibility to reshaping and being incorporated into the fibri

SUBMITTER: Krausser J 

PROVIDER: S-EPMC7777200 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature