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

Abstract

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