Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.21.214072v1?rss=1 Authors: Tian, Y., Liang, R., Kumar, A., Szwedziak, P., Viles, J. H. Abstract: Amyloid-{beta} (A{beta}) monomers assemble into mature fibrils via a range of metastable oligomeric and protofibrillar intermediates. These A{beta} assemblies have been shown to bind to lipid bilayers. This can disrupt membrane integrity and cause a loss of cellular homeostasis, that triggers a cascade of events leading to Alzheimers disease. However, molecular mechanisms of A{beta} cytotoxicity and how the different assembly forms interact with the membrane remain enigmatic. Here we use cryo-electron tomography (cryoET) to obtain three-dimensional nano-scale images of various A{beta} assembly types and their interaction with liposomes. A{beta} oligomers bind extensively to the lipid vesicles, inserting and carpeting the upper-leaflet of the bilayer. Furthermore, curvilinear protofibrils also insert into the bilayer, orthogonally to the membrane surface. A{beta} oligomers concentrate at the interface of vesicles and form a network of A{beta}-linked liposomes. While crucially, monomeric and fibrillar A{beta} have relatively little impact on the membrane. Changes to lipid membrane composition highlights a significant role for GM1-ganglioside in promoting A{beta}-membrane interactions. The different effects of A{beta} assembly forms observed align with the highlighted cytotoxicity reported for A{beta} oligomers. The wide-scale incorporation of A{beta} oligomers and curvilinear protofibrils into the lipid bilayer suggests a mechanism by which membrane integrity is lost. Copy rights belong to original authors. Visit the link for more info