The diagram is divided into six sections, each highlighting different aspects of T-cell mechanics. Section 1, labeled MECHANICS IN DEVELOPMENT, includes T-cell subtypes, organ/tissue of development, and cell cycle. Section 2, labeled MECHANICS OF MIGRATION, covers integrins and cytoskeleton, mechanosensitive ion channels, and amoeboid motility. Section 3, labeled MECHANICS OF ACTIVATION, involves mechanics at the TCR-pMHC, cytoskeletal dynamics, and cytotoxic and effector function. Section 4, labeled MECHANICS AT ENVIRONMENT, includes membrane protrusions, substrate mechanical properties, and surface topography. Section 5, labeled MECHANICS IN DISEASE, addresses mechanical dysregulation such as heterogeneous stiffness, solid stress, acidic pH, and hypoxia. Section 6, labeled IMMUNOTHERAPIES, covers CAR-T therapies, engineered TCR therapies, and nanomedicine. The central image shows T-cells interacting with their environment, illustrating the integration of mechanical and biochemical signals across different scales.
Mechanobiological framework of T-cell function from development to therapy. Schematic representation of the multiscale integration of mechanical and biochemical signals in T cells. Mechanical cues regulate T-cell development (lineage specification and proliferation), migration (amoeboid motility, integrin engagement, cytoskeletal remodeling), and activation (force-dependent TCR-pMHC interactions, signaling, and effector responses). These processes are modulated by environmental features such as substrate stiffness, viscoelasticity, and topography. In disease, mechanical dysregulation of the TME impairs T-cell infiltration and function. Emerging therapeutic strategies exploit these insights to enhance immune responses, including CAR T-cell and eTCR therapies, and nanomedicine approaches targeting biomechanical barriers.