Intercellular mechanical communication drives the directional migration of Jurkat T immune cells.

Although the mechanisms by which chemokines regulate immune responses have been extensively elucidated, the contributions of biophysical mechanical cues to the modulation of immune cell migratory behaviors remain largely unexplored. In this study, we employed a modular co-culture system in which suspension Jurkat T lymphocytes (with RAW264.7 macrophages serving as a positive migratory control) were paired with two force-generating cell types-human airway smooth muscle cells (hASMCs) and human lung adenocarcinoma A549 cells-cultured on type I collagen hydrogels to investigate the effects of intercellular mechanical signals on immune cell migration. Jurkat T cells exhibited directional migration toward force-generating cells on a 2D hydrogel surface, with migratory trajectories consistently oriented toward these cells. Glutaraldehyde-mediated crosslinking of collagen or collagen supplemented with Matrigel, which disrupted cell-cell mechanical interactions, significantly impaired the directional migration of Jurkat T cells. Similar impairment was observed following inhibition of hASMC contractility or culture of force-generating cells on a polystyrene surface, further confirming the role of mechanotaxis in this migratory phenotype. Notably, Jurkat T cells exhibited greater migratory efficiency toward hASMCs than toward A549 cells, a phenomenon likely attributable to cell type-specific intrinsic mechanical properties. Furthermore, 3D culture, in which cells were sandwiched between collagen layers, significantly attenuated the directional migration of Jurkat T cells toward both force-generating cell types. Collectively, these results demonstrate that T cell mechanotaxis is modulated by the intrinsic mechanical phenotype of force-generating cells and the dimensionality of the extracellular matrix microenvironment. These findings indicate that biophysical mechanical cues, independent of yet complementary to chemokine gradients, are potent regulators of directional T cell migration, providing new insights into the emerging field of immunomechanics.