We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies. We present a detailed analysis of the Active Vertex Model to study the mechanics of confluent epithelial tissues and cell monolayers. The model combines the commonly used Vertex Model for describing epithelial tissue mechanics with the active matter dynamics extensively studied in soft matter physics. We utlise an exact mathematical mapping that enables a very efficient numerical implementation using standard methods for simulating particle-based models. System sizes accessible to this model allow us to probe the dynamical motion patterns that occur in tissues over a range of length- and time-scales previously inaccessible to available simulation tools. Our model also includes a number of essential features required to properly describe actual biological systems such as cell growth, cell division and aptotsis, as well as the dynamic boundary of the epithelial sheet. This allows us to study phenomena such as the finger-like protrusions in cell monolayers and processes related to wound healing. The model is implemented into the SAMoS simulation software package and is publically available under a non-restrictive open source licence.

Collective cell migration is a key process during the development of most organisms. It can involve either the migration of closely packed mesenchymal cells that make dynamic contacts with frequently changing neighbour cells, or the migration of epithelial sheets that typically display more stable cell-cell interactions and less frequent changes in neighbours. These collective movements can be controlled by short- or long-range dynamic gradients of extracellular signalling molecules, depending on the number of cells involved and their distance of migration. These gradients are sensed by some or all of the migrating cells and translated into directed migration, which in many settings is further modulated by cell-contact-mediated attractive or repulsive interactions that result in contact-following or contact-inhibition of locomotion, respectively. Studies of collective migration of groups of epithelial cells during development indicate that, in some cases, only leader cells sense and migrate up an external signal gradient, and that adjacent cells follow through strong cell-cell contacts. In this Commentary, I review studies of collective cell migration of differently sized cell populations during the development of several model organisms, and discuss our current understanding of the molecular mechanisms that coordinate this migration.

Primitive streak formation in the chick embryo involves large-scale highly coordinated flows of more than 100,000 cells in the epiblast. These large-scale tissue flows and deformations can be correlated with specific anisotropic cell behaviours in the forming mesendoderm through a combination of light-sheet microscopy and computational analysis. Relevant behaviours include apical contraction, elongation along the apical–basal axis followed by ingression, and asynchronous directional cell intercalation of small groups of mesendoderm cells. Cell intercalation is associated with sequential, directional contraction of apical junctions, the onset, localization and direction of which correlate strongly with the appearance of active myosin II cables in aligned apical junctions in neighbouring cells. Use of class specific myosin inhibitors and gene-specific knockdown shows that apical contraction and intercalation are myosin II dependent and also reveal critical roles for myosin I and myosin V family members in the assembly of junctional myosin II cables.

Proteus mirabilis colonies exhibit striking geometric regularity. Basic microbiological methods and imaging techniques were used to measure periodic macroscopic events in swarm colony morphogenesis. We distinguished three initial phases (lag phase, first swarming phase, and first consolidation phase) followed by repeating cycles of subsequent swarming plus consolidation phases. Each Proteus swarm colony terrace corresponds to one swarming-plus-consolidation cycle. The duration of the lag phase was dependent upon inoculation density in a way that indicated the operation of both cooperative and inhibitory multicellular effects. On our standard medium, the second and subsequent swarm phases displayed structure in the form of internal waves visible with reflected and dark-field illumination. These internal waves resulted from organization of the migrating bacteria into successively thicker cohorts of swarmer cells. Bacterial growth and motility were independently modified by altering the composition of the growth medium. By varying the glucose concentration in the substrate, it was possible to alter biomass production without greatly affecting the kinetics of colony surface area expansion. By varying the agar concentration in the substrate, initial bacterial biomass production was unaffected but colony expansion dynamics were significantly altered. Higher agar concentrations led to slower, shorter swarm phases and longer consolidation phases. Thus, colony growth was restricted by higher agar concentrations but the overall timing of the swarming-plus-consolidation cycles remained constant. None of a variety of factors which had significant effects on colony expansion altered terracing frequencies at 32 degrees C, but the length of the swarming-plus-consolidation cycle was affected by temperature and medium enrichment. Some clinical isolates displayed significant differences in terracing frequencies at 32 degrees C. Our results defined a number of readily quantifiable parameters in swarm colony development. The data showed no connection between nutrient (glucose) depletion and the onset of different phases in swarm colony morphogenesis. Several observations point to the operation of density-dependent thresholds in controlling the transitions between distinct phases.

To test the hypothesis that periodic signals and chemotaxis direct later morphogenesis in Dictyostelium discoideum, we investigated cell behavior and cell movement in slugs. Trails of neutral red-stained prestalk and anterior-like cells were recorded by high-resolution digital image processing. Neutral red-stained anterior-like cells in the prespore zone of slugs move straight forward in the direction of slug migration and, furthermore, show coherent periodic cell movement. In contrast, cells in the prestalk zone move along completely different trajectories. Prestalk cells move perpendicular to the direction of slug migration; that is, they rotate around the tip. The cell movement data show that the chemotactic signal in the slug propagates as a three-dimensional scroll wave in the prestalk zone and as a planar wave in the prespore zone. The different behavior of prestalk and prespore cells is most likely caused by a difference in the oscillatory properties of the two cell types. We provide evidence that the slug stage of Dictyostelium behaves like an excitable system and that a (twisted) scroll wave organizes slug formation and migration.