| Abstract: |
| Lymphocyte activation is an essential step in the adaptive immune response, and involves the binding of specialized receptors with antigen on the surface of antigen presenting cells. This leads to changes in cell morphology and assembly of receptors and signaling proteins into microclusters, which are essential for immune cell activation. During activation, immune cells interact with structures possessing a diverse range of physical properties. We have examined how T cells and B cells respond to physical cues such as stiffness, topography and ligand mobility. I will discuss the roles of the cytoskeleton in the exertion of mechanical stresses that support signaling activation and microcluster assembly. We have used traction force microscopy to measure the forces exerted by T cells during activation on elastic substrates. Forces exerted are largely due to actin dynamics and T cells are mechanosensitive to substrate stiffness. Further, these forces are regulated by microtubule dynamics through Rho activity and myosin filament assembly. Our studies highlight the importance of cytoskeletal forces in T cell receptor activation. More recently, we have examined the role of actin dynamics on forces exerted by cytotoxic T lymphocytes. These studies may have implications for understanding the effectiveness of lymphocytes in killing cancer cells. |
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