Macrophage mechanobiology: from sensing to disease

Objective: Macrophages are highly plastic immune cells that maintain tissue homeostasis through their roles in immune surveillance, repair, and remodeling. Emerging evidence reveals that macrophages, residing in tissues with widely varying stiffness, are profoundly influenced by the mechanical properties of their microenvironment. Methods: Relevant publications on macrophage mechanoregulation published up to January 2026 were identified through systematic searches of PubMed, EMBASE, and Web of Science using combinations of keywords related to macrophages, mechanosensing, mechanotransduction, and mechanical stimuli (e.g., stiffness, stretch, and shear stress). Articles were screened based on relevance to macrophage biology and mechanistic insights. Results: Mechanical cues are sensed through mechanosensors such as Piezo1, TRPV4, and integrins, which integrate these signals to regulate immune surveillance, inflammation, tissue repair, and remodeling. Dysregulation of these pathways contributes to the pathogenesis of multiple diseases, including fibrosis, atherosclerosis, and neurodegeneration. Conclusion: Macrophage mechanobiology represents a critical regulatory axis in tissue homeostasis and disease. Targeting mechanosensing pathways offers promising therapeutic opportunities to modulate inflammation and enhance tissue regeneration.