The stiffness of extracellular matrix in regulating cellular metabolism

Cells interact dynamically with the extracellular matrix (ECM), which provides both structural support and biochemical signals that regulate various cellular processes. Among these, the mechanical properties of the ECM, particularly stiffness, play a crucial role in governing cell differentiation, migration, and survival. Recent studies have highlighted the intricate relationship between ECM stiffness and cellular metabolism, influencing key pathways such as glucose, lipid, and amino acid metabolism. This review explores how ECM stiffness modulates these metabolic processes, emphasizing the underlying mechanotransduction mechanisms. In addition, we discuss emerging techniques that enable the investigation of ECM-mediated force sensing and response, providing new insights into the mechanoregulation of metabolism and its implications in disease and therapy.