This project will use a combination of experiment and theory to test the hypothesis that mechanical forces generated by the cytoskeleton are important for efficient immune response during T cell activation. Forces generated by T cells during signaling activation will be measured and correlated with intracellular dynamics of cytoskeletal proteins and receptor clusters as well as signaling. Computer simulations of the feedback between signaling and force generation will be developed to compare with experimental results on molecular perturbations that interrupt the mechanochemical feedback. This research will provide fundamental insights into the role of physical forces in the biochemical signaling function of lymphocytes. The research project will enhance the understanding of biological systems using experimental and theoretical tools from Physics and Cell Biology. In particular, gaining deeper insights into the way immune cells are activated may facilitate future biomedical advances. A course titled Dynamics of Cells will be developed in which concepts from topics, such as statistical and continuum mechanics, will be used to explain biological processes. A laboratory component will introduce students to basic biophysics techniques and cell biology experiments. Students from disadvantaged socio-economic backgrounds, as well as high school students, especially females from the area high schools, will be encouraged to participate in research. Software developed as part of this research to model actin dynamics and mechanical signaling will be made publicly available.
