Amoeboid Cell Migration through Regular Arrays of Micropillars under Confinement

Abstract

Migrating cells often encounter a wide variety of topographic features—including the presence of obstacles—when navigating through crowded biological environments. Unravelling the impact of topography and crowding on the dynamics of cells is key to better understand many essential physiological processes such as the immune response. We study how migration and search efficiency of HL-60 cells differentiated into neutrophils in quasi two-dimensional environments are influenced by the lateral and vertical confinement and spatial arrangement of obstacles. A microfluidic device is designed to track the cells in confining geometries between two parallel plates with distance h, in which identical micropillars are arranged in regular pillar forests. We find that at each cell-pillar contact event, the cell spends a finite time near the pillar surface, which is independent of the height h and the interpillar spacing e. At low pillar density regime, the directional persistence of cells reduces with decreasing h or e, influencing their diffusivity and first-passage properties. The dynamics is strikingly different at high pillar density regime, where the cells are in simultaneous contact with more than one pillar; the cell velocity and persistence are distinctly higher compared to dilute pillar configurations with the same h. Our simulations reveal that the interplay between cell persistence and cell-pillar interactions can dramatically affect cell diffusivity and, thus, its first-passage properties.