Fig. 6: Load-and-fail mechanism versus differential-transmission mechanism.

a,b, Schematic representations of the load-and-fail mechanism (a) and the differential-transmission mechanism (b). The formation of molecular clutches results in transmission of the force generated by myosin II motors to the substrate, causing its deformation. In the load-and-fail mechanism, when the increasing tension of molecular clutches reaches a certain value, the molecular clutches dissociate in a highly cooperative manner as a result of their high rigidity, which is usually used in conventional molecular-clutch models (a). By contrast, in the models developed in our study (b), molecular clutches exhibit highly elastic properties, which is in good agreement with experiments. This leads to a loss of synchronization of the dissociation of molecular clutches under the myosin II-generated load, and as a result, the molecular-clutch system exhibits a more uniform behaviour, functioning as a differential transmission that mechanically couples the substrate and actin cytoskeleton, which are moving at different speeds. c–e, Stochastic kinetic simulations of the conventional molecular-clutch model (c) and our linear KD (d) and linear WT (e) models. The conventional molecular-clutch model predicts stochastic oscillations between zero and the maximum cell traction on soft substrates (load-and-fail mechanism). By contrast, the linear WT and linear KD models predict much milder fluctuations of the molecular-clutch system around its steady state, with the amplitude of fluctuations being smaller for softer molecular-clutch components (linear WT model) due to the differential-transmission mechanism schematically shown in b.