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bioRxiv · 10.1101/2025.10.03.680352

T Cells Tear Apart Confining Extracellular Matrix Via a Breaststroke-like Motion to Generate Migration Paths

Ha, B.·Xie, P.·Johns, B.·Allan, C.·Korah, M.·Delitto, D.·Bollyky, P.·Torok, N.·Chaudhuri, O.
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Abstract

T cells adeptly migrate through soft tissues to target aberrant cells and regulate immunity. However, how they establish migration paths in confining nanoporous extracellular matrices (ECMs), and why they often fail to do so in dense ECMs that occur during fibrosis and around tumors, remain unclear. Here, we studied T cell migration in confining collagen-rich hydrogels spanning a range of stiffness, viscoelasticity, mechanical plasticity, and shear strength. Strikingly, only shear strength--the stress required for material failure--correlated strongly with migration, challenging the long-held focus on stiffness and pore size in cell motility. During migration, T cells extend actin-rich, finger-like protrusions into the ECM, which then undergo divergent breaststroke-like motion. Thus, T cells tear apart confining matrices using breaststroke-like motion to generate migration paths.

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Ha, B., Xie, P., Johns, B., Allan, C., Korah, M., Delitto, D., Bollyky, P., Torok, N., Chaudhuri, O.. 2025-10-05. T Cells Tear Apart Confining Extracellular Matrix Via a Breaststroke-like Motion to Generate Migration Paths. https://doi.org/10.1101/2025.10.03.680352

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