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bioRxiv · 10.1101/2022.06.08.495291

Subtype-specific single β1 integrin mechanics for activation, mechanotransduction and cytoskeleton remodeling

Jo, M. H.·Li, J.·Jaumouille, V.·Hao, Y.·Coppola, J.·Yan, J.·Waterman, C. M.·Springer, T. A.·Ha, T.
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Abstract

Although integrins are known to be mechano-sensitive 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 4{beta}1 and RGD-binding integrins (V{beta}1 and 5{beta}1) require markedly different tension thresholds to support cell spreading. Furthermore, actin assembled downstream of 4{beta}1 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 V{beta}1 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.

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Jo, M. H., Li, J., Jaumouille, V., Hao, Y., Coppola, J., Yan, J., Waterman, C. M., Springer, T. A., Ha, T.. 2022-06-09. Subtype-specific single β1 integrin mechanics for activation, mechanotransduction and cytoskeleton remodeling. https://doi.org/10.1101/2022.06.08.495291

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