Regulation of Cytoskeletal Dynamics during T Cell Activation by Substrate Stiffness

T lymphocytes are an integral part of the adaptive immune response. The detection of infectious agents critically depends on the interaction of T cells with antigen presenting cells, which have varying mechanical stiffness and complex topological features. It has been recently recognized that T cell activation is regulated both by stiffness of the antigen presenting surface and by cytoskeletal forces which partially arise from actomyosin contractility. However, the relationship between stiffness and the force generating machinery driving T cell activation is not well understood. To address this problem, we characterized actin and myosin dynamics during the activation of Jurkat T cells on stimulatory elastic substrates with variable stiffness using total internal reflection and confocal fluorescence microscopy. Activated T cells exhibited lamellipodial actin and myosin flows at the cell periphery as well as lamellar rings of actomyosin bundles. We have explored the stiffness-dependent organization of these distinct actomyosin structures, flows, and their correlation with the spatiotemporal variation of traction stresses. This study brings insight into the potential role of stiffness in regulating cytoskeletal organization and force generation during T cell activation.