Abstract
Cell migration processes are controlled by sensitive interaction with external cues such as topographic structures of the cell’s environment. Here, we present systematically controlled assays to investigate the specific effects of spatial density and local geometry of topographic structure on amoeboid migration of Dictyostelium discoideum cells. This is realized by well-controlled fabrication of quasi-3D pillar fields exhibiting a systematic variation of inter-pillar distance and pillar lattice geometry. By time-resolved local mean-squared displacement analysis of amoeboid migration, we can extract motility parameters in order to elucidate the details of amoeboid migration mechanisms and consolidate them in a two-state contact-controlled motility model, distinguishing directed and random phases. Specifically, we find that directed pillar-to-pillar runs are found preferably in high pillar density regions, and cells in directed motion states sense pillars as attractive topographic stimuli. In contrast, cell motion in random probing states is inhibited by high pillar density, where pillars act as obstacles for cell motion. In a gradient spatial density, these mechanisms lead to topographic guidance of cells, with a general trend towards a regime of inter-pillar spacing close to the cell diameter. In locally anisotropic pillar environments, cell migration is often found to be damped due to competing attraction by different pillars in close proximity and due to lack of other potential stimuli in the vicinity of the cell. Further, we demonstrate topographic cell guidance reflecting the lattice geometry of the quasi-3D environment by distinct preferences in migration direction. Our findings allow to specifically control amoeboid cell migration by purely topographic effects and thus, to induce active cell guidance. These tools hold prospects for medical applications like improved wound treatment, or invasion assays for immune cells.
Highlights
Amoeboid motion is a efficient form of cell migration, characteristic for several cell types, e.g. stem cells, specific immune cells or metastatic tumor cells
We study the influence of structural properties of the local environment on amoeboid migration of Dd cells in the vegetative state, in the absence of any chemical attractors
We investigate the influence of spatial density and geometry of the environment, independently of the details of the particular substrate adhesion mechanism of the cells
Summary
Amoeboid motion is a efficient form of cell migration, characteristic for several cell types, e.g. stem cells, specific immune cells or metastatic tumor cells. The high efficiency of amoeboid migration is the result of interplay of fast cytoskeletal dynamics and relatively weak, short-lived contacts to the substrate [2,3,4,5,6,7,8]. These mechanisms allow for a rapid response to chemical and mechanical cues in the cells’ environment [9]. Amoeboid migration is observed for neutrophils and leukocytes, migrating towards the source of an inflammation in response to molecular signaling cascades [10]. Dd is both a biologically relevant and experimentally robust model organism to study amoeboid cell migration as a response to environmental cues [12]
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