T-Cell Mechanobiology: Force Sensation, Potentiation, and Translation

A T cell is a sensitive self-referential mechanical sensor. Mechanical forces influence the recognition, activation, differentiation, and function throughout the lifetime of a T cell. T cells constantly perceive and respond to physical stimuli through their surface receptors, cytoskeleton, and subcellular structures. Surface receptors receive physical cues in the form of forces generated through receptor-ligand binding events, which are dynamically regulated by contact tension, shear stress, and substrate rigidity. The resulting mechanotransduction not only influences T-cell recognition and signaling but also possibly modulates cell metabolism and gene expression. Moreover, forces also dynamically regulate the deformation, organization, and translocation of cytoskeleton and subcellular structures, leading to changes in T-cell mobility, migration, and infiltration. However, the roles and mechanisms of how mechanical forces modulate T-cell recognition, signaling, metabolism, and gene expression, are largely unknown and underappreciated. Here, we review recent technological and scientific advances in T-cell mechanobiology, discuss possible roles and mechanisms of T-cell mechanotransduction, and propose new research directions of this emerging field in health and disease.