Mechanosensation: A Catch Bond That Only Hooks One Way

Abstract

Single-molecule force spectroscopy and modeling have revealed that the adhesion molecule vinculin and F-actin form a catch bond that is dependent on the direction of forces along the actin filament. This may underlie the mechanisms by which cells sense directional physical cues.

Figure 1.. Speculative mechanistic model of the two-state vinculin-actin catch bond.

Solid arrows represent force vectors, dotted arrows represent the approximate orientation of the connection between vinculin head (Vh) and vinculin tail (Vt) domains. Left: state 1, the weak binding state. Residues 896–1047 of the crystal structure of Vt in the absence of actin (PDB 1QKR) are displayed in ribbon representation, superimposed on the cryo-EM structure of the Vt-actin complex (not shown). H1 is magenta; H2–H4 are orange. A cryo-EM reconstruction of naked F-actin (EMD 6448) is displayed in light blue. Right: state 2, the strong binding state. Vt from the cryo-EM structure of the Vt-F-actin complex (PDB 3JBI) is displayed in orange ribbon representation. The cryo-EM density map of the complex (EMD 6446) is displayed with the following coloring: Vt helices 1–4, transparent grey; actin, light blue; density corresponding to unfolded H1, magenta.