Intercellular Mechanical Communication Drives Directional Migration of Jurkat T Immune Cells
Abstract
While the regulatory mechanisms of chemokines in orchestrating adaptive and innate 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 experimental system, pairing suspension Jurkat T lymphocytes (with RAW 264.7 macrophages as a positive migratory control) with two distinct force-generating cell types—human airway smooth muscle cells (ASMCs) and human lung adenocarcinoma A549 cells—cultured on 1 mg/mL type I collagen hydrogels, to dissect the regulatory effects of intercellular mechanical signals on the directional migration of immune cells. We observed that Jurkat T cells exhibited robust, targeted directional migration toward force-generating cells on the 2D hydrogel surface, with migratory trajectories consistently oriented toward mechanically active target cells. Glutaraldehyde-mediated crosslinking of collagen matrix or higher-stiffness ~5 mg/mL Matrigel supplemented with 0.5 mg/mL collagen, which ablates cell-cell mechanical interactions, significantly impaired the directional attraction of immune cells, confirming the role of mechanotaxis in this migratory phenotype. Notably, Jurkat T cell migratory efficiency depended on the identity of force-generating cells, with enhanced directional migration toward ASMCs relative to A549 cells, a phenotype likely driven by cell type-specific intrinsic mechanical properties. Furthermore, 3D encapsulation within bulk collagen hydrogels significantly attenuated Jurkat T cell directional migration toward both force-generating cell types, relative to the 2D hydrogel platform. Collectively, our data demonstrate that T cell mechanotaxis is dually modulated by the intrinsic mechanical phenotype of force-generating cells and the dimensionality of the extracellular matrix microenvironment. These findings establish that biophysical mechanical cues, independent of and complementary to canonical chemokine gradients, are potent regulators of directional T cell migration, providing novel mechanistic insights into the emerging field of immunomechanics.
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