IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35173-w.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35173-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35173-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Arventh Velusamy & Radhika Sharma & Sk Aysha Rashid & Hiroaki Ogasawara & Khalid Salaita, 2024. "DNA mechanocapsules for programmable piconewton responsive drug delivery," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Jérôme R D Soiné & Christoph A Brand & Jonathan Stricker & Patrick W Oakes & Margaret L Gardel & Ulrich S Schwarz, 2015. "Model-based Traction Force Microscopy Reveals Differential Tension in Cellular Actin Bundles," PLOS Computational Biology, Public Library of Science, vol. 11(3), pages 1-16, March.
    3. Mitchell S. Wang & Yuesong Hu & Elisa E. Sanchez & Xihe Xie & Nathan H. Roy & Miguel Jesus & Benjamin Y. Winer & Elizabeth A. Zale & Weiyang Jin & Chirag Sachar & Joanne H. Lee & Yeonsun Hong & Minsoo, 2022. "Mechanically active integrins target lytic secretion at the immune synapse to facilitate cellular cytotoxicity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. 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.
    5. Ehsan Akbari & Melika Shahhosseini & Ariel Robbins & Michael G. Poirier & Jonathan W. Song & Carlos E. Castro, 2022. "Low cost and massively parallel force spectroscopy with fluid loading on a chip," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    6. Matthew R. Pawlak & Adam T. Smiley & Maria Paz Ramirez & Marcus D. Kelly & Ghaidan A. Shamsan & Sarah M. Anderson & Branden A. Smeester & David A. Largaespada & David J. Odde & Wendy R. Gordon, 2023. "RAD-TGTs: high-throughput measurement of cellular mechanotype via rupture and delivery of DNA tension probes," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    7. Markus Haake & Beatrice Haack & Tina Schäfer & Patrick N. Harter & Greta Mattavelli & Patrick Eiring & Neha Vashist & Florian Wedekink & Sabrina Genssler & Birgitt Fischer & Julia Dahlhoff & Fatemeh M, 2023. "Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35173-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.