This book focuses on matrix rigidity responses in neurons and fibroblasts. The specific matrix rigidity requirements in different cell types have been correlated to the rigidities of their native tissues in vivo. While fibroblasts spread to the larger areas on rigid than on soft substrates, soft substrates stimulate axon elongation and branching in the primary neurons. In our studies, we described a fibronectin-specific rigidity response pathway, present both in fibroblasts and neurons. Although neurons respond to the FN rigidity in the opposite way to fibroblasts, we suggest that the mechanism of detecting FN rigidity is similar and involves rigidity-dependent RPTP_ recruitment of Fyn, and subsequent p130Cas tyrosine phosphorylation. Once phosphorylated, p130Cas could signal to a variety of different pathways that normally promote growth and not differentiation.