Immunity in motion: The role of mechanics in macrophage biology

The ability of innate immune cells to sense and respond to their physical environment is essential for regulating immune function. Macrophages, key players in inflammation, pathogen defense, and tissue repair, are influenced not only by biochemical cues but also by the mechanical properties of their microenvironment, including extracellular matrix stiffness, shear stress, and cyclic stretch. While the effects of soluble factors, such as cytokines on macrophage behavior are well characterized, the mechanisms underlying macrophage mechanotransduction remain poorly understood. This review synthesizes current understanding of how distinct mechanical forces shape macrophage activation, migration, polarization, and cytokine production. We also explore emerging insights into the roles of mechanosensitive ion channels (e.g., Piezo1, TRPV4), integrins, and cytoskeletal dynamics in transducing mechanical signals into pro- or anti-inflammatory responses. A deeper understanding of these pathways may uncover new therapeutic targets for treating cardiovascular diseases, including atherosclerosis.