This study delivers the first quantitative, single-molecule measurement of force-dependent conformational transitions in vinculin, using high-precision magnetic tweezers and molecular dynamics to reveal a reversible unfolding mechanism at physiologically relevant forces (5–15 pN). It resolves how cells translate nanoscale mechanical cues into biochemical decisions, establishing vinculin as a mechanosensitive force buffer that, via a dynamic feedback loop with talin, stabilizes adhesions and enables substrate stiffness sensing. The resulting quantitative framework is generalizable to other mechanoproteins (e.g., α-catenin, paxillin) and reshapes understanding of supramolecular force transmission by linking piconewton forces, protein elasticity, and emergent cellular behavior. Beyond biology, it advances biophysics and soft-matter physics.
Citation: Sci. Adv. 11, eadt3710, 2025
Authors: X. Liu, J. Liu, Y. Wang, M. Yao, K.B. Baker, B. Klapholz, N.H. Brown, B.T. Goult, J. Yan