Microenvironment stiffness regulates cell cycle

The cell cycle is a highly conserved and ordered process that regulates cell proliferation under physiological and pathological conditions. Among the physical properties of the cellular microenvironment, the extracellular matrix (ECM) stiffness is a crucial regulator of cellular behavior. Emerging research suggests a strong relationship between ECM stiffness and cell cycle progression, although the underlying mechanisms remain unclear. In various diseases, including cancer, neurological disorders, and fibrosis, both ECM stiffness and the cell cycle are tightly involved, thereby influencing disease progression. In addition, ECM stiffness varies across tissues as the disease progresses. This review summarizes current findings on the mechanotransduction pathway through which microenvironmental stiffness regulates the cell cycle across different cell types and stiffness ranges. We also discuss the limitations of the current research and future directions for deepening our understanding of how physical cues in the microenvironment modulate cell cycle control.