Myosin forces remodel F-actin for mechanosensitive protein recognition.

Abstract

Cells interface mechanically with their surroundings through cytoskeleton-linked adhesions^1,2, which enable them to sense physical cues that instruct development and drive diseases such as cancer^3-5. Contractile forces generated by myosin motor proteins^6,7 mediate these mechanical signal transduction processes through unknown protein structural mechanisms. Here we show that force generated by myosin elicits structural changes in actin filaments (F-actin) that modulate binding by the mechanosensitive adhesion protein α-catenin⁸. Using correlative cryo-fluorescence microscopy and cryo-electron tomography, we identify F-actin featuring sinusoidal regions of nanoscale oscillating curvature at cytoskeleton-adhesion interfaces enriched in zyxin, a marker of actin-myosin-generated traction forces⁹. We introduce a reconstitution system for visualizing F-actin in the presence of myosin forces using cryo-electron microscopy, which reveals morphologically similar F-actin supercoils. In simulations, compressive forces that mimic myosin activity produce supercoils, which can be generated by ensembles of asynchronous motors regardless of their directionality. Three-dimensional reconstruction of supercoils uncovers extensive asymmetric remodelling of the helical lattice of F-actin. This is recognized by α-catenin, which binds cooperatively along individual strands, preferentially engaging interfaces that feature extended inter-subunit distances while simultaneously suppressing rotational deviations to regularize the lattice. In sum, we find that myosin forces can deform F-actin, generating a conformational landscape that is detected and reciprocally modulated by a mechanosensitive protein, providing a direct structural glimpse at active force transduction through the cytoskeleton.