Analysis of Multiscale Nuclear Dynamics during Lymphocyte Activation

T cells play an essential role in the adaptive immune response. Through direct interactions via the T cell receptor (TCR), T cells recognize and bind foreign antigens on the surface of antigen presenting cells (APCs), resulting in activation. Following TCR binding and activation, the T cell spreads onto the APC and forms an immune synapse, which is accompanied by changes in cytoskeletal architecture and dynamics as well as nuclear deformation and reorganization. How the mechanical properties of the nucleus, which are governed in part by their chromatin distribution, influence the formation of the immune synapse and thus regulate immune function remains unknown. In this work, we perform high-resolution live cell imaging of T cell nuclei during activation. We tracked individual chromatin loci and overall chromatin flows to characterize dynamics in response to activation and altered chromatin compaction. Our analysis of nuclear dynamics at multiple time and length scales allows us to characterize the restructuring of chromatin architecture and mechanical changes across the nucleus. We find that both T cell activation and modulation of chromatin compaction affect nuclear dynamics on multiple scales, raising important questions about how chromatin dynamics may influence gene expression during early phases of the T cell immune response.