FOCAL ADHESION MECHANOTRANSDUCTION: MOLECULAR EVENTS LEADING TO VINCULIN ACTIVATION

摘要

Vinculin activation and recruitment to focal adhesions is critical to the mechanical reinforcement of cell-extracellular matrix (ECM) connections. The mechanisms of vinculin activation and its interaction with binding partners talin and actin are investigated using molecular dynamics models. The results suggest that a unique cooperative binding mechanism is necessary to activate vinculin. Simulation of vinculin-talin interaction suggests a critical role of hydrophobic insertion while simulation of activated vinculin binding to F-actin suggests electrostatic interactions play a critical role. The results further suggest that both processes of vinculin activation and vinculin binding to its partners are greatly enhanced by a mechanical environment.