Issue 20, 2021

3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography

Abstract

Amyloid-β (Aβ) 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 Alzheimer's disease. However, molecular mechanisms of Aβ 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 Aβ assembly types and their interaction with liposomes. Aβ oligomers and curvilinear protofibrils bind extensively to the lipid vesicles, inserting and carpeting the upper-leaflet of the bilayer. Aβ oligomers concentrate at the interface of vesicles and form a network of Aβ-linked liposomes, while crucially, monomeric and fibrillar Aβ have relatively little impact on the membrane. Changes to lipid membrane composition highlight a significant role for GM1-ganglioside in promoting Aβ-membrane interactions. The different effects of Aβ assembly forms observed align with the highlighted cytotoxicity reported for Aβ oligomers. The wide-scale incorporation of Aβ oligomers and curvilinear protofibrils into the lipid bilayer suggests a mechanism by which membrane integrity is lost.

Graphical abstract: 3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography

Supplementary files

Article information

Article type
Edge Article
Submitted
23 11 2020
Accepted
31 3 2021
First published
31 3 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 6896-6907

3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography

Y. Tian, R. Liang, A. Kumar, P. Szwedziak and J. H. Viles, Chem. Sci., 2021, 12, 6896 DOI: 10.1039/D0SC06426B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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