Topographical guidance of highly-motile cells using cell-sized features

Cells navigate complex environments where they encounter a variety of physical cues. The extracellular topography is such a cue, as a substrate of anisotropically placed, sub-micron sized pillars, was recently shown to induce directed cell migration, a process named topotaxis. Here, we focused on a larger scale, and studied the influence of cell-sized obstacles on highly-motile, persistent cell migration. Using engineered topographies, reminiscent of pores cells squeeze though in vivo, and tracking cell migration, we explored the effects of spacing and obstacle geometry on cell motility. We show that cells undergo long-range topotaxis over large distances by anisotropically placed cell-sized obstacles. Furthermore, we performed active particle simulations, a minimal model for cell motility, to investigate the physics needed to reproduce key features of cell motion in different topographies. Finally, we show that long-range topographic guidance is conserved in chemical gradients, and moreover, the cues, topotaxis and chemotaxis, abide to linear summation, guiding the cell in the direction of both cues combined. Hence, topotaxis offers an independent way to steer cells, which can be exploited as a tool for in vitro applications, like lab on chip diagnosis and tissue engineering.