Intercellular Mechanical Communication Drives Directional Migration of Jurkat T Immune Cells
Abstract
While the mechanisms of chemokines in regulating 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 applied a modular co-culture system, pairing suspension Jurkat T lymphocytes (with RAW 264.7 macrophages as a positive migratory control) with two force-generating cell types—human airway smooth muscle (ASMCs) and human lung adenocarcinoma A549—cultured on type I collagen hydrogels, to dissect the effects of intercellular mechanical signals on migration of immune cells. We observed that Jurkat T cells exhibited directional migration toward force-generating cells on 2D hydrogel surface, with migratory trajectories consistently oriented toward mechanically active target cells. Glutaraldehyde-mediated crosslinking of collagen or Matrigel supplemented with collagen, which ablates cell-cell mechanical interactions, significantly impaired directional attraction of Jurkat T, and so did with inhibited contraction force of ASMCs or cells seeding on glass surface, confirming the role of mechanotaxis in this migratory phenotype. Notably, Jurkat T migratory efficiency was enhanced toward ASMCs relative to A549, a phenotype likely driven by cell type-specific intrinsic mechanical properties. Furthermore,3D encapsulation within bulk collagen hydrogels significantly attenuated Jurkat T directional migration toward both force-generating cells. Collectively, our data demonstrate that T cell mechanotaxis is dually modulated by intrinsic mechanical phenotype of force-generating cells and dimensionality of extracellular matrix microenvironment. These findings indicate that biophysical mechanical cues, independent of and complementary to chemokine gradients, are potent regulators of directional T cell migration, providing new insights into the emerging field of immunomechanics.
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