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N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity

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  • Eva Barcelona-Estaje

    (Advanced Research Centre, University of Glasgow)

  • Mariana A. G. Oliva

    (Advanced Research Centre, University of Glasgow)

  • Finlay Cunniffe

    (Advanced Research Centre, University of Glasgow)

  • Aleixandre Rodrigo-Navarro

    (Advanced Research Centre, University of Glasgow)

  • Paul Genever

    (University of York)

  • Matthew J. Dalby

    (Advanced Research Centre, University of Glasgow)

  • Pere Roca-Cusachs

    (the Barcelona Institute of Technology (BIST)
    University of Barcelona)

  • Marco Cantini

    (Advanced Research Centre, University of Glasgow)

  • Manuel Salmeron-Sanchez

    (Advanced Research Centre, University of Glasgow
    the Barcelona Institute of Technology (BIST)
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

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.

Suggested Citation

  • Eva Barcelona-Estaje & Mariana A. G. Oliva & Finlay Cunniffe & Aleixandre Rodrigo-Navarro & Paul Genever & Matthew J. Dalby & Pere Roca-Cusachs & Marco Cantini & Manuel Salmeron-Sanchez, 2024. "N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53107-6
    DOI: 10.1038/s41467-024-53107-6
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    1. Cheng-han Yu & Nisha Bte Mohd Rafiq & Fakun Cao & Yuhuan Zhou & Anitha Krishnasamy & Kabir Hassan Biswas & Andrea Ravasio & Zhongwen Chen & Yu-Hsiu Wang & Keiko Kawauchi & Gareth E. Jones & Michael P., 2015. "Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
    2. Cheng Zhang & Hongyuan Zhu & Xinru Ren & Bin Gao & Bo Cheng & Shaobao Liu & Baoyong Sha & Zhaoqing Li & Zheng Zhang & Yi Lv & Haohua Wang & Hui Guo & Tian Jian Lu & Feng Xu & Guy M. Genin & Min Lin, 2021. "Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Ovijit Chaudhuri & Justin Cooper-White & Paul A. Janmey & David J. Mooney & Vivek B. Shenoy, 2020. "Effects of extracellular matrix viscoelasticity on cellular behaviour," Nature, Nature, vol. 584(7822), pages 535-546, August.
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