# N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity
**Source**: https://eprints.gla.ac.uk/337328/
**Parent**: https://eprints.gla.ac.uk/view/project_code/303613.html
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# N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity
Barcelona-Estaje, Eva, Oliva, Mariana A.G., [Cunniffe, Finlay](https://eprints.gla.ac.uk/view/author/68098.html), [Rodrigo-Navarro, Aleixandre](https://eprints.gla.ac.uk/view/author/33734.html) [ORCID: https://orcid.org/0000-0002-3786-0464](https://orcid.org/0000-0002-3786-0464), Genever, Paul, [Dalby, Matthew J.](https://eprints.gla.ac.uk/view/author/9268.html) [ORCID: https://orcid.org/0000-0002-0528-3359](https://orcid.org/0000-0002-0528-3359), Roca-Cusachs, Pere, [Cantini, Marco](https://eprints.gla.ac.uk/view/author/30437.html) [ORCID: https://orcid.org/0000-0003-0326-1508](https://orcid.org/0000-0003-0326-1508) and [Salmeron-Sanchez, Manuel](https://eprints.gla.ac.uk/view/author/30067.html) [ORCID: https://orcid.org/0000-0002-8112-2100](https://orcid.org/0000-0002-8112-2100)
(2024)
N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity.
*[Nature Communications](https://eprints.gla.ac.uk/view/journal_volume/Nature_Communications.html)*, 15,
8824.
(doi: [10.1038/s41467-024-53107-6](https://doi.org/10.1038/s41467-024-53107-6))
(PMID:[39394209](https://europepmc.org/abstract/MED/39394209))
(PMCID:[PMC11479646](https://europepmc.org/articles/PMC11479646))
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| | [Text](https://eprints.gla.ac.uk/337328/1/337328.pdf) 337328.pdf - Published Version Available under License [Creative Commons Attribution](http://creativecommons.org/licenses/by/4.0/). 3MB |
## 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.
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| Item Type: | Articles |
| Additional Information: | The work was supported by funding from the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 874889 - HEALIKICK), European Research Council AdG (101054728) and EPSRC through the Transformative Healthcare Technologies Programme Grant ‘Mechanomeds’ (EP/X033554/1). M.C acknowledges funding from the Medical Research Council (MR/S005412/1) and the Royal Society (RGS/R1/231400). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | [Salmeron-Sanchez, Professor Manuel](https://eprints.gla.ac.uk/view/author/30067.html) and [Rodrigo-Navarro, Mr Aleixandre](https://eprints.gla.ac.uk/view/author/33734.html) and [Cunniffe, Finlay](https://eprints.gla.ac.uk/view/author/68098.html) and [Cantini, Dr Marco](https://eprints.gla.ac.uk/view/author/30437.html) and [Dalby, Professor Matthew](https://eprints.gla.ac.uk/view/author/9268.html) |
| Authors: | Barcelona-Estaje, E., Oliva, M. A.G., [Cunniffe, F.](https://eprints.gla.ac.uk/view/author/68098.html), [Rodrigo-Navarro, A.](https://eprints.gla.ac.uk/view/author/33734.html), Genever, P., [Dalby, M. J.](https://eprints.gla.ac.uk/view/author/9268.html), Roca-Cusachs, P., [Cantini, M.](https://eprints.gla.ac.uk/view/author/30437.html), and [Salmeron-Sanchez, M.](https://eprints.gla.ac.uk/view/author/30067.html) |
| College/School: | [College of Medical Veterinary and Life Sciences](https://eprints.gla.ac.uk/view/divisions/20000000/) > [School of Molecular Biosciences](https://eprints.gla.ac.uk/view/divisions/25400000/) [College of Science and Engineering](https://eprints.gla.ac.uk/view/divisions/30000000/) [College of Science and Engineering](https://eprints.gla.ac.uk/view/divisions/30000000/) > [School of Engineering](https://eprints.gla.ac.uk/view/divisions/30300000/) [College of Science and Engineering](https://eprints.gla.ac.uk/view/divisions/30000000/) > [School of Engineering](https://eprints.gla.ac.uk/view/divisions/30300000/) > [Biomedical Engineering](https://eprints.gla.ac.uk/view/divisions/30303000/) |
| Journal Name: | [Nature Communications](https://eprints.gla.ac.uk/view/journal_volume/Nature_Communications.html) |
| Publisher: | Nature Research |
| ISSN: | 2041-1723 |
| ISSN (Online): | 2041-1723 |
| Copyright Holders: | Copyright © 2024 The Authors |
| First Published: | First published in Nature Communications 15:8824 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
| Data DOI: | [10.5525/gla.researchdata.1769](https://doi.org/10.5525/gla.researchdata.1769) |
University Staff: [Request a correction](https://eprints.gla.ac.uk/cgi/request_correction?eprintid=337328) | Enlighten Editors: [Update this record](https://eprints.gla.ac.uk/cgi/users/home?screen=EPrint::View&eprintid=337328)
Funder and Project Information
[Funder and Project Information](#)
[Funder and Project Information](#)
Project Code
Award No
Project Name
Principal Investigator
Funder's Name
Funder Ref
Lead Dept
[307621](https://eprints.gla.ac.uk/view/project_code/307621.html)
HEALIKICK
Manuel Salmeron-Sanchez
[European Commission (EC)](https://eprints.gla.ac.uk/view/funder/European_Commission_=28EC=29.html)
874889
School of Molecular Biosciences
[315918](https://eprints.gla.ac.uk/view/project_code/315918.html)
DEVISE - Engineered viscoelasticity in regenerative microenvironments
Manuel Salmeron-Sanchez
[EPSRC EU Guarantee (EPSRCEU)](https://eprints.gla.ac.uk/view/funder/EPSRC_EU_Guarantee_=28EPSRCEU=29.html)
101054728
ENG - Biomedical Engineering
[318950](https://eprints.gla.ac.uk/view/project_code/318950.html)
Mechanobiology-based medicine - Phase 2
Manuel Salmeron-Sanchez
[Engineering and Physical Sciences Research Council (EPSRC)](https://eprints.gla.ac.uk/view/funder/Engineering_and_Physical_Sciences_Research_Council_=28EPSRC=29.html)
EP/X033554/1
ENG - Biomedical Engineering
[303613](https://eprints.gla.ac.uk/view/project_code/303613.html)
Engineered microenvironments to harvest stem cell response to viscosity for cartilage repair
Marco Cantini
[Medical Research Council (MRC)](https://eprints.gla.ac.uk/view/funder/Medical_Research_Council_=28MRC=29.html)
MR/S005412/1
ENG - Biomedical Engineering
[320080](https://eprints.gla.ac.uk/view/project_code/320080.html)
Harnessing viscoelasticity for regenerative medicine
Marco Cantini
[The Royal Society (ROYSOC)](https://eprints.gla.ac.uk/view/funder/The_Royal_Society_=28ROYSOC=29.html)
RGS/R1/231400
ENG - Biomedical Engineering
Deposit and Record Details
[Deposit and Record Details](#)
[Deposit and Record Details](#)
| | |
| --- | --- |
| ID Code: | 337328 |
| Depositing User: | [Ms Jacqui Brannan](https://eprints.gla.ac.uk/profile/6299) |
| Datestamp: | 14 Oct 2024 16:47 |
| Last Modified: | 08 Jul 2025 11:59 |
| Date of acceptance: | 30 September 2024 |
| Date of first online publication: | 12 October 2024 |
| Date Deposited: | 3 October 2024 |
| Data Availability Statement: | Yes |
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