Immune cells such as natural killer (NK) cells migrate with high speeds of several μm/min through dense tissue, but the traction forces are unknown. We present a method to measure dynamic traction forces of fast migrating cells in non-linear biopolymer matrices. We find that NK cells display bursts of large traction forces that increase with matrix stiffness and facilitate migration through tight constrictions.
To reach targets outside the bloodstream, immune cells can extravasate and migrate through connective tissue. However, in contrast to migrating mesenchymal cells, the importance of matrix adhesion and traction force generation for immune cell migration is not well understood. We use time-lapse confocal reflection microscopy to obtain simultaneous measurements of migration velocity, directional persistence, and cell contractility. While we confirm that immune cells use a non-contractile amoeboid migration mode by default, we also find that NK92 cells as well as ex-vivo expanded NK cells exert substantial acto-myosin driven contractile forces on the extracellular matrix during short contractile phases reaching up to 100nN. Even non-activated primary B, T, NK cells, neutrophils, and monocytes exhibit this burst-like contractile behavior, and NK activation with cytokines increases both the magnitude and frequency of contractile bursts. Importantly, we show that cell speed and directional persistence of NK cells increase during and after these contractile phases, implying that the cells actively use traction forces to overcome steric hindrance and avoid getting stuck in narrow pores of the ECM. Accordingly, reducing cell adhesion to the ECM reduces the fraction of motile cells and their directional persistence, while the remaining motile cells mostly maintain their cell speed. We conclude that steric hindrance can induce a switch in the migration mode of immune cells, from a non-adhesive amoeboid migration mode to a highly contractile migration mode that closely resembles the gliding motion of motile mesenchymal cells.
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