Bridging the gap between single-cell migration and collective dynamics.

Motivated by the wealth of experimental data recently available, we present a cellular-automaton-based modeling framework focussing on high-level cell functions and their concerted effect on cellular migration patterns. Specifically, we formulate a coarse-grained description of cell polarity through self-regulated actin organization and its response to mechanical cues. Furthermore, we address the impact of cell adhesion on collective migration in cell cohorts. The model faithfully reproduces typical cell shapes and movements down to the level of single cells, yet allows for the efficient simulation of confluent tissues. In confined circular geometries, we find that specific properties of individual cells (polarizability; contractility) influence the emerging collective motion of small cell cohorts. Finally, we study the properties of expanding cellular monolayers (front morphology; stress and velocity distributions) at the level of extended tissues.

Emergence and Persistence of Collective Cell Migration on Small Circular Micropatterns.

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.

Critical assessment of the Boltzmann approach to active systems.

Generic models of propelled particle systems posit that the emergence of polar order is driven by the competition between local alignment and noise. Although this notion has been confirmed employing the Boltzmann equation, the range of applicability of this equation remains elusive. We introduce a broad class of mesoscopic collision rules and analyze the prerequisites for the emergence of polar order in the framework of kinetic theory. Our findings suggest that a Boltzmann approach is appropriate for weakly aligning systems but is incompatible with experiments on cluster forming systems.

Longitudinal response of confined semiflexible polymers.

The longitudinal response of single semiflexible polymers to sudden changes in externally applied forces is known to be controlled by the propagation and relaxation of backbone tension. Under many experimental circumstances, realized, for example, in nanofluidic devices or in polymeric networks or solutions, these polymers are effectively confined in a channel- or tubelike geometry. By means of heuristic scaling laws and rigorous analytical theory, we analyze the tension dynamics of confined semiflexible polymers for various generic experimental setups. It turns out that in contrast to the well-known linear response, the influence of confinement on the nonlinear dynamics can largely be described as that of an effective prestress. We also study the free relaxation of an initially confined chain, finding a surprising superlinear ~t(9/8) growth law for the change in end-to-end distance at short times.