A direct computational assessment of vinculin-actin unbinding kinetics reveals catch-bonding behavior.

ABSTRACT: Vinculin forms a catch bond with the cytoskeletal polymer actin, displaying an increased bond lifetime upon force application. Notably, this behavior depends on the direction of the applied force, which has significant implications for cellular mechanotransduction. In this work, we present a comprehensive molecular dynamics simulation study, employing enhanced sampling techniques to investigate the thermodynamic, kinetic, and mechanistic aspects of this phenomenon at physiologically relevant forces. We dissect a catch bond mechanism in which force shifts vinculin between either a weakly or strongly bound state. Our results demonstrate that models for these states have unbinding times consistent with those from single-molecule studies, and suggest that both have some intrinsic catch-bonding

SUBMITTER: Pena Ccoa WJ 

PROVIDER: S-EPMC12130851 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature