Extracellular-matrix mechanics regulate cellular metabolism: A ninja warrior behind mechano-chemo signaling crosstalk

Mechanical forces are the indispensable constituent of environmental cues, such as gravity, barometric pressure, vibration, and contact with bodies, which are involved in pattern and organogenesis, providing mechanical input to tissues and determining the ultimate fate of cells. Extracellular matrix (ECM) stiffness, the slow elastic force, carries the external physical force load onto the cell or outputs the internal force exerted by the cell and its neighbors into the environment. Accumulating evidence illustrates the pivotal role of ECM stiffness in the regulation of organogenesis, maintenance of tissue homeostasis, and the development of multiple diseases, which is largely fulfilled through its systematical impact on cellular metabolism. This review summarizes the establishment and regulation of ECM stiffness, the mechanisms underlying how ECM stiffness is sensed by cells and signals to modulate diverse cell metabolic pathways, and the physiological and pathological significance of the ECM stiffness-cell metabolism axis.