Sinusoidal wavy surfaces for curvature-guided migration of T lymphocytes

Micro/nanofabricated surfaces have been widely used for the study of topography-guided migration of cells. While the current studies mostly utilized micro/nanostructures containing sharp edges, internal tissues guiding migration of cells such as blood and lymphatic vessels, bone cavities, perivascular tracks have smooth microscale topographical structures. To overcome these limitations, we fabricated sinusoidal wavy surfaces with various wavelengths by deep X-ray lithography enabling precise and simultaneous control of amplitudes and wavelengths. Using these surfaces, we systematically studied curvature-guided migration of T cells. The majority of T cells migrated along the concave surfaces of sinusoidal wavy structures and as wavelength increased (or curvature decreased), preference to concave surfaces decreased. Integrin-mediated adhesion augmented the tendency of T cells crawling along grooves of highly curved wavy surfaces. To understand mechanisms of curvature-guided migration of T cells, T cells were treated with small molecule drugs such as blebbistatin and CK636, inhibiting myosin II activity and lamellipodia formation, respectively. While lamellipodia-inhibited T cells frequently crossed ridges, myosin II-inhibited T cells were mostly confined within concave surfaces. These results suggest that lamellipodia regulate local actin polymerization in response to surface curvature to maintain T cells within concave surfaces while myosin II-mediated contractile forces push T cells out of concave surfaces to make T cells less sensitive to surface curvature.