Fig. 2.

Matrix stiffness signaling pathways. Stiffness activates integrin-focal adhesion kinase (FAK) and activated FAK regulate several downstream mechanoresponsive signaling pathways. Pathways such as ERK, AKT, β-catenin, RhoA-ROCK, YAP/TAZ play major roles in stiffness mediated characteristics. In stiff ECM, YAP and TAZ are activated and accumulate in the nucleus, whereas in physiological stiffness, they are suppressed and localized in the cytoplasm. The transcriptional coactivators YAP and TAZ lack a DNA-binding domain. Hence, nuclear YAP/TAZ binds to TEAD and regulates the activation of several target genes involved in cell migration, proliferation, anti-apoptotic processes, and stemness