Healthy Tissue: An illustration of healthy tissue showing T cells migrating through the extracellular matrix (ECM) fibers. Tight junctions with normal deformation and tissue-resident memory T cells are visible. Fibroblasts and antigen-presenting cells are also present. Perivascular traction forces are indicated. Tumor Microenvironment: An illustration of the tumor microenvironment showing increased stiffness, high interstitial fluid pressure, imbalanced ionic strength, acidic pH, and hypoxia. T cells are trapped in the stroma, and cancer-associated fibroblasts are present. Soft cancer cells are also shown. Chronic Inflammation: An illustration of chronic inflammation showing increased local pressure and temperature, fibrosis, increased local stiffness, and increased T-cell concentration. Aging: An illustration of aging tissue showing impaired migration, smaller traction forces, high ECM stiffness, and impaired extravasation.
Mechanobiological landscape of healthy and diseased tissues. In homeostatic conditions, tissues contain migrating and TRM interacting with other cell types such as fibroblasts and dendritic cells. T cells traffic through blood and lymphatic vessels and crawl within the ECM by generating traction forces. In tumors, the microenvironment exhibits altered biophysical properties that impair T-cell migration and effector function. Chronic inflammation promotes fibrosis and swelling, reinforcing T-cell recruitment, but perpetuating tissue damage. Aging is characterized by increased ECM stiffness and reduced T-cell deformability, leading to impaired interstitial migration. Red F symbols indicate regions where mechanical forces are particularly important.