Pseudomonas aeruginosa is a ubiquitous bacterium that survives in many environments, including as an acute and chronic pathogen in humans. Substantial evidence shows that P. aeruginosa behavior is affected by its motility, and appendages known as flagella and type IV pili (TFP) are known to confer such motility. The role these appendages play when not facilitating motility or attachment, however, is unclear. Here we discern a passive intercellular role of TFP during flagellar-mediated swarming of P. aeruginosa that does not require TFP extension or retraction. We studied swarming at the cellular level using a combination of laboratory experiments and computational simulations to explain the resultant patterns of cells imaged from in vitro swarms. Namely, we used a computational model to simulate swarming and to probe for individual cell behavior that cannot currently be otherwise measured. Our simulations showed that TFP of swarming P. aeruginosa should be distributed all over the cell and that TFP−TFP interactions between cells should be a dominant mechanism that promotes cell−cell interaction, limits lone cell movement, and slows swarm expansion. This predicted physical mechanism involving TFP was confirmed in vitro using pairwise mixtures of strains with and without TFP where cells without TFP separate from cells with TFP. While TFP slow swarm expansion, we show in vitro that TFP help alter collective motion to avoid toxic compounds such as the antibiotic carbenicillin. Thus, TFP physically affect P. aeruginosa swarming by actively promoting cell−cell association and directional collective motion within motile groups to aid their survival.he bacterium Pseudomonas aeruginosa is a ubiquitous organism that is a known opportunistic pathogen, causing both chronic and acute infections in susceptible populations, including individuals with cystic fibrosis or burn wounds, or Intensive Care Unit patients (1). Among questions that remain unanswered for nonobligate pathogens like P. aeruginosa is how these bacteria initiate infections after entering the host from the environment. Given that P. aeruginosa is among many bacteria that grow as a biofilm during infection, there is a need to understand how individual cells coordinate in space with each other to colonize new surfaces and subsequently transition to stationary biofilms.Many organisms coordinate their movement as a population, emerging as self-organized swarming groups. Even the untrained eye would note the coordinated swarming behavior of fish, birds, and insects. Many bacteria also exhibit collective motion by swarming over surfaces in a coordinated manner to move unimpeded at the same time (2-4). Our knowledge of the specific actions used by individual cells during collective motion is limited; the behavior of single cells within a dense population is difficult to discern experimentally. Previous attempts to study bacterial collective behavior have used computational models to test mechanisms hypothesized to influence collective motion, including directional r...

Mitotic rounding during cell division is critical for preventing daughter cells from inheriting an abnormal number of chromosomes, a condition that occurs frequently in cancer cells. Cells must significantly expand their apical area and transition from a polygonal to circular apical shape to achieve robust mitotic rounding in epithelial tissues, which is where most cancers initiate. However, how cells mechanically regulate robust mitotic rounding within packed tissues is unknown. Here, we analyze mitotic rounding using a newly developed multi-scale subcellular element computational model that is calibrated using experimental data. Novel biologically relevant features of the model include separate representations of the sub-cellular components including the apical membrane and cytoplasm of the cell at the tissue scale level as well as detailed description of cell properties during mitotic rounding. Regression analysis of predictive model simulation results reveals the relative contributions of osmotic pressure, cell-cell adhesion and cortical stiffness to mitotic rounding. Mitotic area expansion is largely driven by regulation of cytoplasmic pressure. Surprisingly, mitotic shape roundness within physiological ranges is most sensitive to variation in cell-cell adhesivity and stiffness. An understanding of how perturbed mechanical properties impact mitotic rounding has important potential implications on, amongst others, how tumors progressively become more genetically unstable due to increased chromosomal aneuploidy and more aggressive.

Mitotic rounding during cell division is critical for preventing daughter cells from inheriting an abnormal number of chromosomes, a condition that occurs frequently in cancer cells. Cells must significantly expand their apical area and transition from a polygonal to circular apical shape to achieve robust mitotic rounding in epithelial tissues, which is where most cancers initiate. However, how cells mechanically regulate robust mitotic rounding within packed tissues is unknown. Here, we analyze mitotic rounding using a newly developed multi-scale subcellular element computational model that is calibrated using experimental data. Novel biologically relevant features of the model include separate representations of the sub-cellular components including the apical membrane and cytoplasm of the cell at the tissue scale level as well as detailed description of cell properties during mitotic rounding. Regression analysis of predictive model simulation results reveals the relative contributions of osmotic pressure, cell-cell adhesion and cortical stiffness to mitotic rounding. Mitotic area expansion is largely driven by regulation of cytoplasmic pressure. Surprisingly, mitotic shape roundness within physiological ranges is most sensitive to variation in cell-cell adhesivity and stiffness. An understanding of how perturbed mechanical properties impact mitotic rounding has important potential implications on, amongst others, how tumors progressively become more genetically unstable due to increased chromosomal aneuploidy and more aggressive.peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/037820 doi: bioRxiv preprint first posted online 3 Author Summary Mitotic rounding (MR) during cell division which is critical for the robust segregation of chromosomes into daughter cells, plays important roles in tissue growth and morphogenesis, and is frequently perturbed in cancerous cells. Mechanisms of MR have been investigated in individual cultured cells, but mechanisms regulating MR in tissues are still poorly understood. We developed and calibrated an advanced subcellular element-based computational model called Epi-Scale that enables quantitative testing of hypothesized mechanisms governing epithelial cell behavior within the developing tissue microenvironment. Regression analysis of predictive model simulation results reveals the relative contributions of osmotic pressure, cell-cell adhesion and cortical stiffness to mitotic rounding and establishes a novel mechanism for ensuring robustness in mitotic rounding within densely packed epithelia.peer-reviewed)

The presence and significance of active topological defects is increasingly realised in diverse biological and biomimetic systems. We introduce a continuum model of polar active matter, based on conservation laws and symmetry arguments, that recapitulates both polar and apolar (nematic) features of topological defects in active turbulence. Using numerical simulations of the continuum model, we demonstrate the emergence of both half- and full-integer topological defects in polar active matter. Interestingly, we find that crossover from active turbulence with half- to full-integer defects can emerge with the coexistence region characterized by both defect types. These results put forward a minimal, generic framework for studying topological defect patterns in active matter which is capable of explaining the emergence of half-integer defects in polar systems such as bacteria and cell monolayers, as well as predicting the emergence of coexisting defect states in active matter.

Swarming groups of bacteria coordinate their behavior by self-organizing as a population to move over surfaces in search of nutrients and optimal niches for colonization. Many open questions remain about the cues used by swarming bacteria to achieve this self-organization. While chemical cue signaling known as quorum sensing is well described, swarming bacteria often act and coordinate on time scales that could not be achieved via these extracellular quorum sensing cues. Here, cell-cell contact-dependent protein exchange is explored as a mechanism of intercellular signaling for the bacterium Myxococcus xanthus. Detailed biologically calibrated computational model is used to study how M. xanthus optimizes the connection rate between cells and maximizes spread of an extracellular protein within the population. The maximum rate of protein spreading is observed for cells that reverse direction optimally for swarming. Cells that reverse too slowly or too fast fail to spread extracellular protein efficiently. In particular, a specific range of cell reversal frequencies was observed to maximize the cell-cell connection rate and minimize the time of protein spreading. Furthermore, our findings suggest that pre-designed motion reversal can be employed to enhance the collective behavior of biological synthetic active systems.