Amyloid-? oligomers have a profound detergent-like effect on lipid membrane bilayers, imaged by atomic force and electron microscopy.

ABSTRACT: The ability of amyloid-? peptide (A?) to disrupt membrane integrity and cellular homeostasis is believed to be central to Alzheimer's disease pathology. A? is reported to have various impacts on the lipid bilayer, but a clearer picture of A? influence on membranes is required. Here, we use atomic force and transmission electron microscopies to image the impact of different isolated A? assembly types on lipid bilayers. We show that only oligomeric A? can profoundly disrupt the bilayer, visualized as widespread lipid extraction and subsequent deposition, which can be likened to an effect expected from the action of a detergent. We further show that A? oligomers cause widespread curvature and discontinuities within lipid vesicle membranes. In contrast, this detergent-like effect was not observed for A? monomers and fibers, although A? fibers did laterally associate and embed into the upper leaflet of the bilayer. The marked impact of A? oligomers on membrane integrity identified here reveals a mechanism by which these oligomers may be cytotoxic.

SUBMITTER: Bode DC 

PROVIDER: S-EPMC6514634 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature