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 nov 2020
Accepted
31 mrt 2021
First published
31 mrt 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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