Nanotopography modulates cytoskeletal organization and dynamics during T cell activation.

ABSTRACT

Exposure to MHC-antigen complexes on the surface of antigen-presenting cells (APCs) activates T cells, inducing the formation of the immune synapse (IS). Antigen detection at the APC surface is thus a critical step in the adaptive immune response. The physical properties of antigen-presenting surfaces encountered by T cells in vivo are believed to modulate T cell activation and proliferation. Although stiffness and ligand mobility influence IS formation, the effect of the complex topography of the APC surface on this process is not well understood. Here we investigate how nanotopography modulates cytoskeletal dynamics and signaling during the early stages of T cell activation using high-resolution fluorescence microscopy on nanofabricated surfaces with parallel nanoridges of different spacings. We find that although nanoridges reduce the maximum spread area as compared with cells on flat surfaces, the ridges enhance the accumulation of actin and the signaling kinase ZAP-70 at the IS. Actin polymerization is more dynamic in the presence of ridges, which influence the directionality of both actin flows and microtubule (MT) growth. Our results demonstrate that the topography of the activating surface exerts both global effects on T cell morphology and local changes in actin and MT dynamics, collectively influencing T cell signaling.