Cells-ECM mechanical interaction: taking advantage of nonlinearities for mechanosensing.*

Most viable cells are anchored to the extracellular matrix (ECM) and can detect its rigidity 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. 

Following this idea, we use a fiber network model to perform numerical experiments mimicking cells probing locally the ECM’s mechanical response. 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.