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Force-FAK signaling coupling at individual focal adhesions coordinates mechanosensing and microtissue repair

Author

Listed:
  • Dennis W. Zhou

    (Georgia Institute of Technology
    Georgia Institute of Technology)

  • Marc A. Fernández-Yagüe

    (Georgia Institute of Technology
    Georgia Institute of Technology)

  • Elijah N. Holland

    (Georgia Institute of Technology
    Georgia Institute of Technology)

  • Andrés F. García

    (Georgia Institute of Technology)

  • Nicolas S. Castro

    (Georgia Institute of Technology)

  • Eric B. O’Neill

    (Georgia Institute of Technology
    Georgia Institute of Technology)

  • Jeroen Eyckmans

    (Boston University
    Harvard University)

  • Christopher S. Chen

    (Boston University
    Harvard University)

  • Jianping Fu

    (University of Michigan)

  • David D. Schlaepfer

    (University of California, San Diego)

  • Andrés J. García

    (Georgia Institute of Technology
    Georgia Institute of Technology)

Abstract

How adhesive forces are transduced and integrated into biochemical signals at focal adhesions (FAs) is poorly understood. Using cells adhering to deformable micropillar arrays, we demonstrate that traction force and FAK localization as well as traction force and Y397-FAK phosphorylation are linearly coupled at individual FAs on stiff, but not soft, substrates. Similarly, FAK phosphorylation increases linearly with external forces applied to FAs using magnetic beads. This mechanosignaling coupling requires actomyosin contractility, talin-FAK binding, and full-length vinculin that binds talin and actin. Using an in vitro 3D biomimetic wound healing model, we show that force-FAK signaling coupling coordinates cell migration and tissue-scale forces to promote microtissue repair. A simple kinetic binding model of talin-FAK interactions under force can recapitulate the experimental observations. This study provides insights on how talin and vinculin convert forces into FAK signaling events regulating cell migration and tissue repair.

Suggested Citation

  • Dennis W. Zhou & Marc A. Fernández-Yagüe & Elijah N. Holland & Andrés F. García & Nicolas S. Castro & Eric B. O’Neill & Jeroen Eyckmans & Christopher S. Chen & Jianping Fu & David D. Schlaepfer & Andr, 2021. "Force-FAK signaling coupling at individual focal adhesions coordinates mechanosensing and microtissue repair," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22602-5
    DOI: 10.1038/s41467-021-22602-5
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    Cited by:

    1. A. Mills & N. Aissaoui & D. Maurel & J. Elezgaray & F. Morvan & J. J. Vasseur & E. Margeat & R. B. Quast & J. Lai Kee-Him & N. Saint & C. Benistant & A. Nord & F. Pedaci & G. Bellot, 2022. "A modular spring-loaded actuator for mechanical activation of membrane proteins," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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