Fig. 6. Proposed molecular mechanism of FN-specific reinforcement and rigidity response in hippocampal neurons. In RPTP^+/+ neurons, matrix rigidity triggers force-dependent activation of the RPTP, followed by activation of Fyn, which consequently phosphorylates stretch-sensitive p130Cas. This results in the recruitment of the focal-contact proteins causing the reinforcement of the growth-cone–substrate links. This reinforcement has a negative effect on the neurite extension. On the soft matrices, the force exerted by the actin-myosin network in response to matrix rigidity, does not reach a threshold critical for the reinforcement of the FN-cytoskeleton bonds and subsequent focal-contact formation. Thus, the neurite extension is stimulated on soft matrices.