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

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.