Migration of T Cells on Surfaces Containing Complex Nanotopography

Abstract

T cells navigate complex microenvironments to initiate and modulate antigen-specific immune responses. While recent intravital microscopy study revealed that migration of T cells were guided by various tissue microstructures containing unique nanoscale topographical structures, the effects of complex nanotopographical structures on the migration of T cells have not been systematically studied. In this study, we fabricated surfaces containing nanoscale zigzag structures with various side lengths and turning angles using UV-assisted capillary force lithography and motility of T cells on zigzag patterned surfaces was studied. Motility of T cells was mostly affected by the turning angle, not by the side length, of the zigzag structures. In particular, motility behaviors of T cells near interfaces formed by turning points of zigzag patterns were significantly affected by turning angles. For obtuse turning angles, most of the T cells smoothly crossed the interfaces, but as the turning angle decreased, a substantial fraction of the T cells migrated along the interfaces. When the formation of lamellipodia, thin sheet-like structures typically generated at the leading edges of migrating cells by actin polymerization-driven membrane protrusion, was inhibited by an Arp2/3 inhibitor CK-636, a substantial fraction of T cells on those surfaces containing zigzag patterns with an acute turning angle were trapped at the interfaces formed by the turning points of the zigzag patterns. This result suggests that thin, wide lamellipodia at the leading edges of T cells play critical roles in motility of T cells in complex topographical microenvironments.