|
Résumé |
Living cells sense the rigidity of their environment and adapt their activity to it. In particular, Cells cultured on elastic substrates align their shape and their traction forces along the direction of highest stiffness, and preferably migrate towards stiffer regions. While numerous studies investigated the role of adhesion complexes in rigidity sensing, less is known about the contribution of acto-myosin based contractility.
Here we used a custom-made single cell technique to measure the traction force as well as the speed of shortening of isolated myoblasts deflecting microplates of variable stiffness. The rate of force generation increased with increasing stiffness and followed a Hill-type force-velocity relationship. Hence, cell response to stiffness was similar to muscle adaptation to load, reflecting the force-dependent kinetics of myosin binding to actin. These results reveal an unexpected mechanism of rigidity sensing, whereby the contractile acto-myosin units themselves can act as sensors. This mechanism may translate anisotropy in substrate rigidity into anisotropy in cytoskeletal tension, and could thus coordinate local activity of adhesion complexes and guide cell migration along rigidity gradients.
In order to further test these ideas, we improved the parallel microplates technique to allow us to change, in real time, the stiffness faced by a single cell. Experiments were carried out as follows. First, we let a cell spread and pull on a plate of a given stiffness k1 while recording its traction force. Then the stiffness was suddenly (in $\approx0.1$ second) tuned to a higher value k2. We found that single cell contractility was instantaneously adapted to the change in plate stiffness. In particular, the rate of force generation increased, in real time, with increasing stiffness. Such an instantaneous response could hardly be explained by chemical transduction pathways. It would rather suggest that early cell response to stiffness could be purely mechanical. |
