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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.Competing Interest StatementThe authors have declared no competing interest.
Many biological active agents respond to gradients of environmental cues by redirecting their motion. Besides the well-studied prominent examples such as photo- and chemotaxis, there has been considerable recent interest in topotaxis, i.e.\ the ability to sense and follow topographic environmental cues. We numerically investigate the topotaxis of active agents moving in regular arrays of circular pillars. While a trivial topotaxis is achievable through a spatial gradient of obstacle density, here we show that imposing a gradient in the characteristics of agent-obstacle interaction can lead to an effective topotaxis in an environment with a spatially uniform density of obstacles. As a proof of concept, we demonstrate how a gradient in the angle of sliding around pillars -- as e.g.\ observed in bacterial dynamics near surfaces -- breaks the spatial symmetry and biases the direction of motion. We provide an explanation for this phenomenon based on effective reflection at the imaginary interface between pillars with different sliding angles. Our results are of technological importance for design of efficient taxis devices.
Many biological active agents respond to gradients of environmental cues by redirecting their motion. In addition to the well-studied prominent examples such as phototaxis and chemotaxis, there has been considerable recent interest in topotaxis, i.e., the ability to sense and follow topographic environmental cues. A trivial topotaxis is achievable through a spatial gradient of obstacle density, though over limited length scales. Here, we introduce a type of topotaxis based on sliding of particles along obstacles—as observed, e.g., in bacterial dynamics near surfaces. We numerically demonstrate how imposing a gradient in the angle of sliding along pillars breaks the spatial symmetry and biases the direction of motion, resulting in an efficient topotaxis in a uniform pillar park. By repeating blocks of pillars with a strong gradient of sliding angle, we propose an efficient method for guiding particles over arbitrary long distances. We provide an explanation for this spectacular phenomenon based on effective reflection at the borders of neighboring blocks. Our results are of technological and medical importance for design of efficient taxis devices for living agents.
Migrating cells often encounter a wide variety of topographic features—including the presence of obstacles—when navigating through crowded biological environments. Unraveling 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 the impact of geometrical cues on ameboid migration of HL-60 cells differentiated into neutrophils. A microfluidic device is designed to track the cells in confining geometries between two parallel plates with distance , in which identical micropillars are arranged in regular pillar forests with pillar spacing . We observe that the cells are temporarily captured near pillars, with a mean contact time that is independent of and . By decreasing the vertical confinement , we find that the cell velocity is not affected, while the persistence reduces; thus, cells are able to preserve their velocity when highly squeezed but lose the ability to control their direction of motion. At a given , we show that by decreasing the pillar spacing in the weak lateral confinement regime, the mean escape time of cells from effective local traps between neighboring pillars grows. This effect, together with the increase of cell-pillar contact frequency, leads to the reduction of diffusion constant . By disentangling the contributions of these two effects on in numerical simulations, we verify that the impact of cell-pillar contacts on cell diffusivity is more pronounced at smaller pillar spacing.
CD8+ cytotoxic T lymphocytes (CTL) and natural killer cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (also known as target cells). To find their targets, they have to navigate and migrate through complex biological microenvironments, a key component of which is the extracellular matrix (ECM). The mechanisms underlying killer cell?s navigation are not well understood. To mimic an ECM, we use a matrix formed by different collagen concentrations and analyze migration trajectories of primary human CTLs. Different migration patterns are observed and can be grouped into three motility types: slow, fast, and mixed. The dynamics are well described by a two-state persistent random walk model, which allows cells to switch between slow motion with low persistence and fast motion with high persistence. We hypothesize that the slow motility mode describes CTLs creating channels through the collagen matrix by deforming and tearing apart collagen fibers and that the fast motility mode describes CTLs moving within these channels. Experimental evidence supporting this scenario is presented by visualizing migrating T cells following each other on exactly the same track and showing cells moving quickly in channel-like cavities within the surrounding collagen matrix. Consequently, the efficiency of the stochastic search process of CTLs in the ECM should strongly be influenced by a dynamically changing channel network produced by the killer cells themselves.
