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Cytoskeletal forces during signaling activation in Jurkat T-cells
Authors:King Lam Hui  Lakshmi Balagopalan  Lawrence E. Samelson  Arpita Upadhyaya
Affiliation:Carnegie Mellon University;aDepartment of Physics, University of Maryland, College Park, MD 20742;cInstitute for Physical Sciences and Technology, University of Maryland, College Park, MD 20742;bLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Abstract:T-cells are critical for the adaptive immune response in the body. The binding of the T-cell receptor (TCR) with antigen on the surface of antigen-presenting cells leads to cell spreading and signaling activation. The underlying mechanism of signaling activation is not completely understood. Although cytoskeletal forces have been implicated in this process, the contribution of different cytoskeletal components and their spatial organization are unknown. Here we use traction force microscopy to measure the forces exerted by Jurkat T-cells during TCR activation. Perturbation experiments reveal that these forces are largely due to actin assembly and dynamics, with myosin contractility contributing to the development of force but not its maintenance. We find that Jurkat T-cells are mechanosensitive, with cytoskeletal forces and signaling dynamics both sensitive to the stiffness of the substrate. Our results delineate the cytoskeletal contributions to interfacial forces exerted by T-cells during activation.
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