Diverse interactions among species within bacterial colonies lead to intricate spatiotemporal dynamics, which can affect their growth and survival. Here, we describe the emergence of complex structures in a colony grown from mixtures of motile and non-motile bacterial species on a soft agar surface. Time-lapse imaging shows that non-motile bacteria 'hitchhike' on the motile bacteria as the latter migrate outward. The non-motile bacteria accumulate at the boundary of the colony and trigger an instability that leaves behind striking flower-like patterns. The mechanism of the front instability governing this pattern formation is elucidated by a mathematical model for the frictional motion of the colony interface, with friction depending on the local concentration of the non-motile species. A more elaborate two-dimensional phase-field model that explicitly accounts for the interplay between growth, mechanical stress from the motile species, and friction provided by the non-motile species, fully reproduces the observed flower-like patterns.
Cells and the path of least resistance: For processes encompassing proper embryonic development, adult homeostasis, tumor cell dissemination, and immunity, certain cells must translocate from their site of origin. Migrating cells navigate physical features of their microenvironment; however, the in vivo importance of tissue topography for pathfinding is mostly unknown. Studying fruit flies, Dai et al. used border cells within the ovarian egg chamber to study path selection. Live imaging, genetics, mathematical modeling, and simulations showed that tissue microtopography provides an energetically favorable path of least resistance, whereas chemoattractants supply orthogonal guidance information and cell-cell adhesion contributes traction. The results provide insight into how cells integrate and prioritize topographical, adhesive, and chemoattractant cues to choose one path among many. Science , this issue p. 987
Eukaryotic cells can migrate using different modes, ranging from amoeboid-like, during which actin filled protrusions come and go, to keratocyte-like, characterized by a stable morphology and persistent motion. How cells can switch between these modes is not well understood but waves of signaling events are thought to play an important role in these transitions. Here we present a simple two-component biochemical reaction-diffusion model based on relaxation oscillators and couple this to a model for the mechanics of cell deformations. Different migration modes, including amoeboid-like and keratocyte-like, naturally emerge through transitions determined by interactions between biochemical traveling waves, cell mechanics and morphology. The model predictions are explicitly verified by systematically reducing the protrusive force of the actin network in experiments using Dictyostelium discoideum cells. Our results indicate the importance of coupling signaling events to cell mechanics and morphology and may be applicable in a wide variety of cell motility systems.
During migration, eukaryotic cells can continuously change their three-dimensional morphology, resulting in a highly dynamic and complex process. Further complicating this process is the observation that the same cell type can rapidly switch between different modes of migration. Modelling this complexity necessitates models that are able to track deforming membranes and that can capture the intracellular dynamics responsible for changes in migration modes. Here we develop an efficient three-dimensional computational model for cell migration, which couples cell mechanics to a simple intracellular activator–inhibitor signalling system. We compare the computational results to quantitative experiments using the social amoebaDictyostelium discoideum. The model can reproduce the observed migration modes generated by varying either mechanical or biochemical model parameters and suggests a coupling between the substrate and the biomechanics of the cell.
3 March 2021 in Proceedings of the National Academy of Sciences
Significance: The spatial organization of ECM fibers biases the polarization and migration of cancer cells, a phenomenon known as contact guidance which is directly linked to the clinical outcome of cancers. In physiological conditions, ECM fibers do not align perfectly in parallel. Therefore, we study the morphological and migrational response of breast cancer cells to ECM fibers aligned to various degrees. We identify the cell’s aspect ratio as an integrated biomarker that determines its sensitivity to contact guidance cues. We also find that the level of ECM alignment modulates transitions between cells of differing morphology. Taken together, we show that cells integrate complex mechanical cues to determine their morphodynamics, thereby controlling polarization and migration in 3D ECM.