Talin folding as the tuning fork of cellular mechanotransduction

Significance Talin is an adaptor protein that transduces mechanical signals into biochemical cues by recruiting a network of protein ligands in a force-dependent way. These force cues have a complex nature, oscillate in time with different frequency components, and are often embedded in noise. However, most assays to explore the mechanics of force-sensing proteins rely on simple perturbations, such as constant or ramped forces. Here, we use our magnetic tweezers design to subject single talin domains to oscillatory forces and external mechanical noise. We show that talin ignores random external fluctuations but synchronizes its folding dynamics with force oscillations in a frequency-dependent way. We hypothesize that this finely tuned response could underpin talin force-sensing properties.