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Single-molecule characterization of subtype-specific β1 integrin mechanics

Myung Hyun Jo, Jing Li, Valentin Jaumouillé, Yuxin Hao, Jessica Coppola, Jiabin Yan, Clare M. Waterman, Timothy A. Springer () and Taekjip Ha ()
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Myung Hyun Jo: Johns Hopkins University
Jing Li: Program in Cellular and Molecular Medicine, Boston Children’s Hospital
Valentin Jaumouillé: Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health
Yuxin Hao: Program in Cellular and Molecular Medicine, Boston Children’s Hospital
Jessica Coppola: Institute for Protein Innovation Harvard Institutes of Medicine
Jiabin Yan: Program in Cellular and Molecular Medicine, Boston Children’s Hospital
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
Taekjip Ha: Johns Hopkins University

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35173-w

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