The spontaneous formation of vortices is a hallmark of collective cellular activity. Here, we study the onset and persistence of coherent angular motion as a function of the number of cells N confined in circular micropatterns. We find that the persistence of coherent angular motion increases with N but exhibits a pronounced discontinuity accompanied by a geometric rearrangement of cells to a configuration containing a central cell. Computer simulations based on a generalized Potts model reproduce the emergence of vortex states and show in agreement with experiment that their stability depends on the interplay of the spatial arrangement and internal polarization of neighboring cells. Hence, the distinct migrational states in finite size ensembles reveal significant insight into the local interaction rules guiding collective migration.
Collective cell migration in epithelial tissues resembles fluid-like behavior in time-lapse recordings. In the last years, hydrodynamic velocity fields in living matter have been studied intensely. The emergent properties were remarkably similar to phenomena known from active soft matter systems. Here, we review migration experiments of large cellular ensembles as well as of mesoscopic cohorts in micro-structured environments. Concepts such as diffusion, velocity correlations, swirl strength and polarization are metrics to quantify the cellular dynamics both in experiments as well as in computational simulations. We discuss challenges relating collective migration to single cell and oligocellular behavior as well as linking the phenotypic parameters to the underlying cytoskeleton dynamics and signaling networks. This article is part of a Special Issue entitled: Mechanobiology.
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.Migrating cells play a pivotal role in morphogenesis 1 , immune responses 2 , and cancer metastasis 3 . Their style of motion, often assigned as crawling, is powered by complex cytoskeletal rearrangements that deform and propel the cell. On solid surfaces, eukaryotic cells extend protrusions, which attach to the substrate and are then actively retracted, thus dragging the cell forward. The formation of the leading protrusion of a migrating cell, the lamellipodium, is driven by actin polymerization, while adhesion and contraction are predominantly regulated by integrin-based focal adhesions and the actomyosin apparatus 4,5 . Coupling of focal adhesion complexes to the cytoskeletal network in turn reinforces actin assembly and hence lamellipodia extension 6 . The complex interplay between actomyosin contractility and focal adhesions, which are capable of sensing and transducing chemical and mechanical cues in the extracellular environment, renders the cell sensitive to external stimuli such as the composition and rigidity of the extracellular matrix (ECM) and the underlying substrate 7,8 .In recent studies, 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 9-11 to coarse grained approaches in which individual cells are resembled by sets of pixels 12-14 or interacting, self-propelled geometrical objects [15][16][17] . Many of these models are able to reproduce the basic ...
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