Séminaire 'matière molle' : Estelle BERTHIER (LMU Munich)

"cells-ECM mechanical interaction:
taking advantage of nonlinearities for mechanosensing"
par Estelle BERTHIER

Most viable cells are anchored to the extracellular matrix (ECM) and can detect the rigidity of their surrounding ECM by mechanically probing the network (mechanosensing). However, the ECM is a highly heterogeneous structure with large mechanical fluctuations: the local stiffness exhibits a broad distribution.

Yet, cells respond robustly to the mechanical cues of the ECM and adequately regulate their behavior. Hence, it remains unclear what strategies cells employ to accurately interpret mechanical guiding cues of such a heterogeneous environment. Cells can generate forces large enough to trigger ECM deformations that deviate from linear elasticity. Recent experimental findings indicate that when large forces are non-linearly deforming the network, the mechanical fluctuations become less sensitive to the network disorder. These observations indicate that non-linear effects could be extremely important for cellular mechanosensation, both as a way to induce strong cues for cell-cell communication and to enable representative measures of local stiffness.

Following this idea, we use a fiber network model to perform numerical experiments mimicking cells probing locally the ECM's mechanical response. We generate depleted networks of fibers with nonlinear constitutive law to describe the ECM and we perform local stiffness measures by applying local forces. In agreement with the experiments, we observe that the signal to noise ratio strongly increases in the nonlinear regime, independently of the network's details. We rationalize these results by identifying an emerging length-scale that grows with the applied force in the nonlinear regime and sets the mechanical response of the probe.