Abstract
T cells migrate through soft tissues to target infected and abnormal cells and regulate immunity. T cell migration is typically studied in microfluidic devices or other contexts where there is a pre-existing migration path; how they create paths in confining nanoporous extracellular matrices (ECM), such as can occur during fibrosis and around tumors, remains unclear. Here, we studied T cell migration in confining collagen-rich matrices with a range of stiffness, viscoelasticity, mechanical plasticity, and shear strength, or the stress at which the material fails. Strikingly, only shear strength, the stress at which a material fails, not stiffness or viscoelasticity, correlates with migration. During migration, T-cells extend thin actin-rich, finger-like protrusions into the ECM, which then undergo a divergent breaststroke-like motion. Thus, T cells tear apart confining matrices using a breaststroke-like motion to generate migration paths.