Nuclear morphology and chromatin organization modulate T cell cytoskeletal remodeling and immune synapse formation.

T cell activation is characterized by rapid reorganization of the actin cytoskeleton and cell spreading on the antigen presenting cell. The T cell nucleus occupies a large fraction of the cell volume, and its mechanical properties are likely to act as a key determinant of activation. However, the contribution of nuclear mechanics to T cell spreading and activation is not well understood. Mechanical rigidity of lymphocyte nuclei is conferred by chromatin compaction and dense packing of heterochromatin. We find that nuclear deformation and increased chromatin compaction accompany T cell spreading, in T cells. Reducing chromatin compaction leads to increased cell spread area and nuclear deformation, while diminishing accumulation and peripheral enrichment of F-actin at the immune synapse. In contrast, enhanced chromatin compaction reduced spread area and nuclear deformation, which was accompanied by increased peripheral F-actin organization at the immune synapse. These findings suggest a reciprocal interaction between chromatin compaction and actin cytoskeletal organization. We identified SUN proteins and myosin as critical elements through which chromatin compaction orchestrates actin morphology and cell shape, facilitating T cell adaptation to antigen-presenting surfaces of varying stiffness. These results emphasize the crucial role of chromatin compaction in T cell activation, underlining the mechanical relationship between the nucleus and the cytoskeleton during immune responses, and suggest new avenues for understanding T cell mechano-responsiveness.