Barcelona-Estaje, Eva, Oliva, Mariana A G, Cunniffe, Finlay et al. (6 more authors) (2024) N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity. Nature Communications. 8824. ISSN 2041-1723
Abstract
Mesenchymal stem cells (MSCs) interact with their surroundings via integrins, which link to the actin cytoskeleton and translate physical cues into biochemical signals through mechanotransduction. N-cadherins enable cell-cell communication and are also linked to the cytoskeleton. This crosstalk between integrins and cadherins modulates MSC mechanotransduction and fate. Here we show the role of this crosstalk in the mechanosensing of viscosity using supported lipid bilayers as substrates of varying viscosity. We functionalize these lipid bilayers with adhesion peptides for integrins (RGD) and N-cadherins (HAVDI), to demonstrate that integrins and cadherins compete for the actin cytoskeleton, leading to an altered MSC mechanosensing response. This response is characterised by a weaker integrin adhesion to the environment when cadherin ligation occurs. We model this competition via a modified molecular clutch model, which drives the integrin/cadherin crosstalk in response to surface viscosity, ultimately controlling MSC lineage commitment.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024. The Author(s). |
Keywords: | Cadherins/metabolism,Integrins/metabolism,Viscosity,Mesenchymal Stem Cells/metabolism,Humans,Mechanotransduction, Cellular,Lipid Bilayers/metabolism,Cell Adhesion,Actin Cytoskeleton/metabolism,Cell Communication,Animals,Oligopeptides/metabolism |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 17 Oct 2024 08:56 |
Last Modified: | 08 Nov 2024 01:28 |
Published Version: | https://doi.org/10.1038/s41467-024-53107-6 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-024-53107-6 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:218530 |