How do mechanical forces impact macrophages in the processes of mechanosensing and mechanotransduction?

Macrophages are sensitive cells to various external mechanical forces in the environment, such as stretch, shear, and pressure. Mechanical forces can be recognized by mechanical signal receptors on the cell surface, such as cell adhesion molecules and ion channels, and transformed into intracellular biological signals, in turn activating different signaling pathways and thereby regulating the phagocytosis, migration, and polarization of macrophages. The phenomenon in which macrophages transform into different activated phenotypes and perform different functions under varying environmental stimuli is also known as macrophage polarization. In this review, we discuss the roles of mechanically sensitive integrins and ion channels in the mechanical signal sensing of macrophages. We expound on several downstream signaling pathways closely related to integrins and ion channels, such as the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) pathways, which have made good research progress. In addition, we summarize some in vitro experiments on the regulation of macrophage polarization by external mechanical forces, some current cell models for macrophages in vitro, and some commonly used force application devices, with the aim to provide convenience for future in vitro research on macrophages. This paper offers a deep understanding of the mechanical sensitivity and conduction mechanisms of macrophages, which can provide new ideas for the treatment of human diseases.