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3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography
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 fo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153238/ https://www.ncbi.nlm.nih.gov/pubmed/34123318 http://dx.doi.org/10.1039/d0sc06426b |
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author | Tian, Yao Liang, Ruina Kumar, Amit Szwedziak, Piotr Viles, John H. |
author_facet | Tian, Yao Liang, Ruina Kumar, Amit Szwedziak, Piotr Viles, John H. |
author_sort | Tian, Yao |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8153238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-81532382021-06-11 3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography Tian, Yao Liang, Ruina Kumar, Amit Szwedziak, Piotr Viles, John H. Chem Sci Chemistry 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. The Royal Society of Chemistry 2021-03-31 /pmc/articles/PMC8153238/ /pubmed/34123318 http://dx.doi.org/10.1039/d0sc06426b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Tian, Yao Liang, Ruina Kumar, Amit Szwedziak, Piotr Viles, John H. 3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography |
title | 3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography |
title_full | 3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography |
title_fullStr | 3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography |
title_full_unstemmed | 3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography |
title_short | 3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography |
title_sort | 3d-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153238/ https://www.ncbi.nlm.nih.gov/pubmed/34123318 http://dx.doi.org/10.1039/d0sc06426b |
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