RT Journal Article SR Electronic T1 Bridging the gap between single-cell migration and collective dynamics JF bioRxiv FD Cold Spring Harbor Laboratory SP 548677 DO 10.1101/548677 A1 Florian Thüroff A1 Andriy Goychuk A1 Matthias Reiter A1 Erwin Frey YR 2019 UL http://biorxiv.org/content/early/2019/03/02/548677.abstract AB A wealth of experimental data relating to the emergence of collective cell migration as one proceeds from the behavioral dynamics of small cohorts of cells to the coordinated migratory response of cells in extended tissues is now available. Integrating these findings into a mechanistic picture of cell migration that is applicable across such a broad range of system sizes constitutes a crucial step towards a better understanding of the basic factors that determine the emergence of collective cell motion. Here we present a cellular-automaton-based modeling framework, which focuses on the integration of high-level cell functions and their concerted effect on cellular migration patterns. In particular, we adopt a top-down approach to incorporate a coarse-grained description of cell polarity and its response to mechanical cues, and address the impact of cell adhesion on collective migration in cell groups. We demonstrate that the model faithfully reproduces typical cell shapes and movements down to the level of single cells, yet is computationally efficient enough to allow for the simulation of (currently) up to 𝒪(104) cells. To develop a mechanistic picture that illuminates the relationship between cell functions and collective migration, we present a detailed study of small groups of cells in confined circular geometries, and discuss the emerging patterns of collective motion in terms of specific cellular properties. Finally, we apply our computational model at the level of extended tissues, and investigate stress and velocity distributions, as well as front morphologies, in expanding cellular sheets.