Random traction yielding transition in epithelial tissues

We investigate how randomly oriented cell traction forces lead to fluidisation in a vertex model of epithelial tissues. We find that the fluidisation occurs at a critical value of the traction force magnitude $F_c$. We show that this transition exhibits critical behaviour, similar to the yielding transition of sheared amorphous solids. However, we find that it belongs to a different universality class, even though it satisfies the same scaling relations between critical exponents established in the yielding transition of sheared amorphous solids. Our work provides a fluidisation mechanism through active force generation that could be relevant in biological tissues

Type IV pili interactions promote intercellular association and moderate swarming of Pseudomonas aeruginosa

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.National Institutes of HealthIndiana Clinical and Translational Sciences Institut

Mechanics of cell integration in vivo

During embryonic development, regeneration and homeostasis, cells have to physically integrate into their target tissues, where they ultimately execute their function. Despite a significant body of research on how mechanical forces instruct cellular behaviors within the plane of an epithelium, very little is known about the mechanical interplay at the interface between migrating cells and their surrounding tissue, which has its own dynamics, architecture and identity. Here, using quantitative in vivo imaging and molecular perturbations, together with a theoretical model, we reveal that multiciliated cell (MCC) precursors in the Xenopus embryo form dynamic filopodia that pull at the vertices of the overlying epithelial sheet to probe their stiffness and identify the preferred positions for their integration into the tissue. Moreover, we report a novel function for a structural component of vertices, the lipolysis-stimulated lipoprotein receptor (LSR), in filopodia dynamics and show its critical role in cell intercalation. Remarkably, we find that pulling forces equip the MCCs to remodel the epithelial junctions of the neighboring tissue, enabling them to generate a permissive environment for their integration. Our findings reveal the intricate physical crosstalk at the cell-tissue interface and uncover previously unknown functions for mechanical forces in orchestrating cell integration

Reversals and collisions optimize protein exchange in bacterial swarms

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. A detailed biologically calibrated computational model is used to study how M. xanthus optimizes the connection rate between cells and maximizes the 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 predesigned motion reversal can be employed to enhance the collective behavior of biological synthetic active systems

Potential energy functions in the Epi-Scale model.

<p>Potential energy functions in the Epi-Scale model.</p

Quantitation of relative sensitivity of mitotic area expansion and roundness to adhesion, stiffness and pressure changes within the physiological property space.

<p>Sensitivity estimation of (A) (<i>A</i>_<i>mit</i>/<i>A</i>_<i>inter</i>) and (B) <i>R</i>_<i>norm</i> to small perturbation in the three mitotic parameter set points, , , and Δ<i>P</i>. Sensitivity was estimated from the reduced RSM model described in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005533#pcbi.1005533.g007" target="_blank">Fig 7C–7F</a> after stepwise model regression (p-value cutoff of 0.01). (C) Proposed mechanical regulatory network defined for “physiological ranges” within the parameter ranges defined by the CCD (Run 2, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005533#pcbi.1005533.g007" target="_blank">Fig 7A</a>) that summarizes the local sensitivity analysis. Cell adhesivity, an increase in , slightly inhibits area expansion and strongly inhibits roundness. Membrane stiffness, inhibits area expansion and promotes roundness. Mitotic area expansion is most sensitive to variation in the mitotic pressure change (Δ<i>P</i>), but pressure has little effect on roundness over the calibrated physiological ranges.</p

Dynamics of mitotic rounding.

<p>(A-A‴) Time-lapse confocal images of cell undergoing mitosis in the wing disc with E-cadherin:GFP-labeled cell boundaries. Scale bar is 5 μm. Arrows indicate daughter cells. (B-D‴) Time series from Epi-Scale simulation of a cell undergoing mitosis and division with illustration of: (B-B‴) adhesive spring stiffness, (C-C‴) cortical spring stiffness, and (D-D‴) internal pressure, respected to their interphase values. (E-F) Comparison of size and roundness of mitotic cells with experimental data for the <i>Drosophila</i> wing disc. Arrow represents mitotic cell in B-D. A t-test comparing the means of computational simulations and experiments result in p = 0.72 for cell area ratio and p = 0.76 for normalized roundness of mitotic cells.</p

Epithelial mechanics and workflow outline.

<p>(A) Apical surface of epithelial cells within the <i>Drosophila</i> wing imaginal disc that are marked by E-cadherin tagged with fluorescent GFP (DE-cadherin::GFP). Multiple cells within the displayed region are undergoing mitotic rounding with a noticeable decrease in fluorescent intensities of E-Cadherin. (B) Experimental image of cross-section of wing disc marking levels of actomyosin (Myosin II::GFP). (C) Cartoon abstraction of epithelial cells, which are polarized with apical and basal sides. Actomyosin and mechanical forces during mitotic rounding are primarily localized near the apical surface. (D) At the molecular scale, the boundary between cells consists of a lipid bilayer membrane for each cell, E-cadherin molecules that bind to each other through homophilic interactions, and adaptor proteins that connect the adhesion complexes to an underlying actomyosin cortex that provides tensile forces along the rim of apical areas of cells. (E) The graphical workflow of the computational modeling setup, calibration, verification and predictions. Arrows indicate mitotic cells. Scale bars are 10 micrometers.</p