Abstract
Quantification and discrimination of pharmaceutical and disease-related effects on cell migration requires detailed characterization of single-cell motility. In this context, micropatterned substrates that constrain cells within defined geometries facilitate quantitative readout of locomotion. Here, we study quasi-one-dimensional cell migration in ring-shaped microlanes. We observe bimodal behavior in form of alternating states of directional migration (run state) and reorientation (rest state). Both states show exponential lifetime distributions with characteristic persistence times, which, together with the cell velocity in the run state, provide a set of parameters that succinctly describe cell motion. By introducing PEGylated barriers of different widths into the lane, we extend this description by quantifying the effects of abrupt changes in substrate chemistry on migrating cells. The transit probability decreases exponentially as a function of barrier width, thus specifying a characteristic penetration depth of the leading lamellipodia. Applying this fingerprint-like characterization of cell motion, we compare different cell lines, and demonstrate that the cancer drug candidate salinomycin affects transit probability and resting time, but not run time or run velocity. Hence, the presented assay allows to assess multiple migration-related parameters, permits detailed characterization of cell motility, and has potential applications in cell biology and advanced drug screening.
Highlights
Migrating cells play a pivotal role in morphogenesis[1], immune responses[2], and cancer metastasis[3]
We observed that cells confined in a lane of this width exhibited a morphology closely resembling that of cells migrating on open 2D surfaces, but were sufficiently constrained to ensure that migration was directed along the lane only (Fig. 1b)
By applying a nuclear stain to track the positions of individual cells on the pattern, we found that these phenotypes tend to correlate with distinct migratory behaviors
Summary
Migrating cells play a pivotal role in morphogenesis[1], immune responses[2], and cancer metastasis[3]. Various theoretical models for cell migration have been proposed and implemented These implementations range from molecular level approaches, which describe cell migration in terms of internal reaction diffusion dynamics[9,10,11] to coarse grained approaches in which individual cells are resembled by sets of pixels[12,13,14] or interacting, self-propelled geometrical objects[15,16,17]. Phenomenological models that include dynamic switching between two different modes of migration often capture the observed migration patterns better, and provide more detailed insights into cellular behavior[31,32,33] The emergence of such bimodality is predicted by theoretical approaches which assume a coupling between actin dynamics and the diffusion of cell internal polarity cues[34]
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