Extracellular matrix geometry regulates T cell migration mode

Most of what we know about cell migration stems from studies using mesenchymal cells on stiff substrates. Immune cells, however, use a different mode of migration known as amoeboid migration which allows them to move significantly faster, with less adhesion, through more complex environments. Immune cells are one of the few cells in the body that are naturally exposed to a wide variety of microenvironments. Previous reports have established that immune cells are able to migrate in the absence of integrins, the protein at the foundation of adhesions. Other reports have suggested, however, that adhesion plays a normal role in regulating immune cell migration in tissue. We therefore hypothesize that immune cells can adapt their migration from adhesion independent to adhesion dependent in response to their environment. To test our hypothesis, we have constructed a variety of ways to confine immune cells and measure both their ability to migrate and the forces they generate in this process. We find that the forces are several orders of magnitude smaller than those measured in mesenchymal cells like fibroblasts and take on a different distribution. Our results provide important insights into the mechanical processes underlying this alternative form of migration.