To determine a relevant probing mechanism for mechanosensation, we simulated the mechanical interactions between a cell and its surrounding environment. We investigated mechanosensation from the perspective of a cell as an ideal mechanosensor inside a disordered matrix. For that purpose, we built a computational model describing both the matrix, via modelling the mechanics of a disordered network of nonlinear fibers, and the cell, modelled as a force applied locally on the network. We measured the stiffness of the network at this cell scale by probing the network at various locations and compared these measurements to the macroscopic modulus of the same network.
The local stiffness measurements revealed a striking behavior. At low forces, the stiffness measured is independent of the applied force and vary strongly from one location to another in the network: cells can only acquire unreliable information about the mechanical landscape of their environment. Remarkably, as the force is increased the local stiffness that cells could measure inside a fibrous matrix becomes reliable: the probing force sets the measured stiffness, this measured stiffness becomes increasingly robust to local network fluctuations and strongly correlated to the macroscopic modulus of the networks. We confirmed these behaviors via experimental measurements performed using optical tweezers in reconstituted biopolymers. Therefore, at low force a single mechanical meaurement is a poor estimator of the network’s average mechanical properties: mechanosensing is strongly limited by structural heterogeneities. By contrast, the local mechanical response of fiber networks becomes largely insensitive to structural disorder at large force and captures the global network properties.
In this large force regime, we identified the emergence of a growing region over which nonlinearities develop. In this section of the network, the distribution of forces is drastically different: a subnetwork of ropes carries most of the load and these tensed fibers are surrounded by compressed buckled bonds. By looking at the density of buckled bonds, we determined the nonlinear region length-scale and showed that this length increases with the imposed force. Because of the emergence of a tensed subnetwork in this region, this section of the network is much stiffer than its surroundings. We confirmed experimentally the emergence of this stiffened nonlinear region by measuring the stiffness at various locations in the wake of contractile cells. Using the observed growth of the stiffened region, we built a scaling argument that adequately explains the measured stiffness fluctuations at large forces.
