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Single-molecule characterization of subtype-specific β1 integrin mechanics

Author

Listed:
  • Myung Hyun Jo

    (Johns Hopkins University)

  • Jing Li

    (Program in Cellular and Molecular Medicine, Boston Children’s Hospital
    Harvard Medical School)

  • Valentin Jaumouillé

    (Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health
    Simon Fraser University)

  • Yuxin Hao

    (Program in Cellular and Molecular Medicine, Boston Children’s Hospital
    Harvard Medical School)

  • Jessica Coppola

    (Institute for Protein Innovation Harvard Institutes of Medicine
    The Scripps Research Institute)

  • Jiabin Yan

    (Program in Cellular and Molecular Medicine, Boston Children’s Hospital
    Harvard Medical School)

  • Clare M. Waterman

    (Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health)

  • Timothy A. Springer

    (Program in Cellular and Molecular Medicine, Boston Children’s Hospital
    Harvard Medical School)

  • Taekjip Ha

    (Johns Hopkins University
    Johns Hopkins University
    Johns Hopkins University
    Howard Hughes Medical Institute)

Abstract

Although integrins are known to be mechanosensitive and to possess many subtypes that have distinct physiological roles, single molecule studies of force exertion have thus far been limited to RGD-binding integrins. Here, we show that integrin α4β1 and RGD-binding integrins (αVβ1 and α5β1) require markedly different tension thresholds to support cell spreading. Furthermore, actin assembled downstream of α4β1 forms cross-linked networks in circularly spread cells, is in rapid retrograde flow, and exerts low forces from actin polymerization. In contrast, actin assembled downstream of αVβ1 forms stress fibers linking focal adhesions in elongated cells, is in slow retrograde flow, and matures to exert high forces (>54-pN) via myosin II. Conformational activation of both integrins occurs below 12-pN, suggesting that post-activation subtype-specific cytoskeletal remodeling imposes the higher threshold for spreading on RGD substrates. Multiple layers of single integrin mechanics for activation, mechanotransduction and cytoskeleton remodeling revealed here may underlie subtype-dependence of diverse processes such as somite formation and durotaxis.

Suggested Citation

  • Myung Hyun Jo & Jing Li & Valentin Jaumouillé & Yuxin Hao & Jessica Coppola & Jiabin Yan & Clare M. Waterman & Timothy A. Springer & Taekjip Ha, 2022. "Single-molecule characterization of subtype-specific β1 integrin mechanics," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35173-w
    DOI: 10.1038/s41467-022-35173-w
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    References listed on IDEAS

    as
    1. Pontus Nordenfelt & Hunter L. Elliott & Timothy A. Springer, 2016. "Coordinated integrin activation by actin-dependent force during T-cell migration," Nature Communications, Nature, vol. 7(1), pages 1-15, December.
    2. Yun Zhang & Chenghao Ge & Cheng Zhu & Khalid Salaita, 2014. "DNA-based digital tension probes reveal integrin forces during early cell adhesion," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
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