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.
Highlights
T cells are immune cells playing a central role in antigenspecific immune responses
Preparation of the Nanoscale Zigzag Structures To study how the motility of T cells is affected by complex nanotopography, we fabricated nanoscale zigzag structures using UV-assisted capillary force lithography (CFL) with UV curable polymer poly(urethane acrylate) (PUA) on glass coverslips as shown in Fig. 1A [20]
Nanostructured PUA surfaces were coated with 10 mg/mL of ICAM-1, a ligand for lymphocyte function-associated antigen 1 (LFA-1) that is one of major integrins of T cells
Summary
To successfully mount antigen-specific immune responses, T cells must migrate to the right place and encounter their partners [1] They become activated by interacting with antigen-presenting cells presenting antigens specific for their T cell receptors in secondary lymphoid organs such as a spleen and lymph nodes, and they perform effector functions by contacting pathogen-harboring cells or transformed cells in peripheral tissues. Multi-photon microscopy performed over the last decade has allowed us to understand how T cells migrate in search for their interaction partners in vivo [3,4] Overall, they migrate rapidly with a peak velocity of 25 mm/min in a rather random fashion to maximize the scanning area [5]. While the effect of soluble factor on directional migration of T cells has been extensively studied using various in vitro model systems such as agarose gel [10], Boyden chambers [11], and microfluidic channels [12], relatively less attention has been paid to the effects of nanotopography on motility of T cells
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