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The surface tension of living cells and tissues originates from the generation of nonequilibrium active stresses within the cell cytoskeleton. Here, using laser ablation, we generate gradients in the surface tension of cellular aggregates as models of simple tissues. These gradients of active surface stress drive large-scale and rapid toroidal motion. Subsequently, the motions spontaneously reverse as stresses reaccumulate and cells return to their original positions. Both forward and reverse motions resemble Marangoni flows in viscous fluids. However, the motions are faster than the timescales of viscoelastic relaxation, and the surface tension gradient is proportional to mechanical strain at the surface. Further, due to active stress, both the surface tension gradient and surface strain are dependent upon the volume of the aggregate. These results indicate that surface tension can induce rapid and highly correlated elastic deformations in the maintenance of tissue shape and configuration.

Coordinated and cooperative motion of cells is essential for embryonic development, tissue morphogenesis, wound healing and cancer invasion. A predictive understanding of the emergent mechanical behaviors in collective cell motion is challenging due to the complex interplay between cell-cell interactions, cell-matrix adhesions and active cell behaviors. To overcome this challenge, we develop a predictive cellular vertex model that can delineate the relative roles of substrate rigidity, tissue mechanics and active cell properties on the movement of cell collectives. We apply the model to the specific case of collective motion in cell aggregates as they spread into a two-dimensional cell monolayer adherent to a soft elastic matrix. Consistent with recent experiments, we find that substrate stiffness regulates the driving forces for the spreading of cellular monolayer, which can be pressure-driven or crawling-based depending on substrate rigidity. On soft substrates, cell monolayer spreading is driven by an active pressure due to the influx of cells coming from the aggregate, whereas on stiff substrates, cell spreading is driven primarily by active crawling forces. Our model predicts that cooperation of cell crawling and tissue pressure drives faster spreading, while the spreading rate is sensitive to the mechanical properties of the tissue. We find that solid tissues spread faster on stiff substrates, with spreading rate increasing with tissue tension. By contrast, the spreading of fluid tissues is independent of substrate stiffness and is slower than solid tissues. We compare our theoretical results with experimental results on traction force generation and spreading kinetics of cell monolayers, and provide new predictions on the role of tissue fluidity and substrate rigidity on collective cell motion., Comment: revised paper title, more references added

We investigate the structural, vibrational, and mechanical properties of jammed packings of deformable particles with shape degrees of freedom in three dimensions (3D). Each 3D deformable particle is modeled as a surface-triangulated polyhedron, with spherical vertices whose positions are determined by a shape-energy function with terms that constrain the particle surface area, volume, and curvature, and prevent interparticle overlap. We show that jammed packings of deformable particles without bending energy possess low-frequency, quartic vibrational modes, whose number decreases with increasing asphericity and matches the number of missing contacts relative to the isostatic value. In contrast, jammed packings of deformable particles with non-zero bending energy are isostatic in 3D, with no quartic modes. We find that the contributions to the eigenmodes of the dynamical matrix from the shape degrees of freedom are significant over the full range of frequency and shape parameters for particles with zero bending energy. We further show that the ensemble-averaged shear modulus $\langle G \rangle$ scales with pressure $P$ as $\langle G \rangle \sim P^{\beta}$, with $\beta \approx 0.75$ for jammed packings of deformable particles with zero bending energy. In contrast, $\beta \approx 0.5$ for packings of deformable particles with non-zero bending energy, which matches the value for jammed packings of soft, spherical particles with fixed shape. These studies underscore the importance of incorporating particle deformability and shape change when modeling the properties of jammed soft materials.

Soft, amorphous solids such as tissues, foams, and emulsions are composed of deformable particles. However, the effect of single-particle deformability on the collective behavior of soft solids is still poorly understood. We perform numerical simulations of two-dimensional jammed packings of explicitly deformable particles to study the mechanical response of model soft solids. We find that jammed packings of deformable particles with excess shape degrees of freedom possess low-frequency quartic vibrational modes that stabilize the packings even though they possess fewer interparticle contacts than the nominal isostatic value. Adding intra-particle constraints can rigidify the particles, but these particles undergo a buckling transition and gain an effective shape degree of freedom when their preferred perimeter is above a threshold value. We find that the mechanical response of jammed packings of deformable particles with shape degrees of freedom differs significantly from that of jammed packings of rigid-shape particles, which emphasizes the importance of particle deformability in modelling soft solids., Comment: 12 pages total, 6 main figures, 4 appendices, 5 appendix figures

Living and non-living active matter consumes energy at the microscopic scale to drive emergent, macroscopic behavior including traveling waves and coherent oscillations. Recent work has characterized non-equilibrium systems by their total energy dissipation, but little has been said about how dissipation manifests in distinct spatiotemporal patterns. We introduce a novel measure of irreversibility we term the entropy production factor (EPF) to quantify how time reversal symmetry is broken in field theories across scales. We use the EPF to characterize a dynamical phase transition in simulations of the Brusselator, a prototypical biochemically motivated non-linear oscillator. The EPF quantifies the distribution of irreversibility across spatiotemporal frequencies as the Brusselator transitions from local to global coherent oscillations, bounding the energetic cost to establish spatially synchronized biochemical oscillations., Comment: 21 pages main, 24 pages SM, 14 figures (5 main, 9 supplementary)

Collective cell migration in cohesive units is vital for tissue morphogenesis, wound repair, and immune response. While the fundamental driving forces for collective cell motion stem from contractile and protrusive activities of individual cells, it remains unknown how their balance is optimized to maintain tissue cohesiveness and the fluidity for motion. Here we present a cell-based computational model for collective cell migration during wound healing that incorporates mechanochemical coupling of cell motion and adhesion kinetics with stochastic transformation of active motility forces. We show that a balance of protrusive motility and actomyosin contractility is optimized for accelerating the rate of wound repair, which is robust to variations in cell and substrate mechanical properties. This balance underlies rapid collective cell motion during wound healing, resulting from a tradeoff between tension mediated collective cell guidance and active stress relaxation in the tissue.

How cells with diverse morphologies and cytoskeletal architectures modulate their mechanical behaviors to drive robust collective motion within tissues is poorly understood. During wound repair within epithelial monolayers in vitro, cells coordinate the assembly of branched and bundled actin networks to regulate the total mechanical work produced by collective cell motion. Using traction force microscopy, we show that the balance of actin network architectures optimizes the wound closure rate and the magnitude of the mechanical work. These values are constrained by the effective power exerted by the monolayer, which is conserved and independent of actin architectures. Using a cell-based physical model, we show that the rate at which mechanical work is done by the monolayer is limited by the transformation between actin network architectures and differential regulation of cell-substrate friction. These results and our proposed molecular mechanisms provide a robust quantitative model for how cells collectively coordinate their non-equilibrium behaviors to dynamically regulate tissue-scale mechanical output., Comment: 34 pages, 6 figures

The actin cytoskeleton is an active semi-flexible polymer network whose non-equilibrium properties coordinate both stable and contractile behaviors to maintain or change cell shape. While myosin motors drive the actin cytoskeleton out-of-equilibrium, the role of myosin-driven active stresses in the accumulation and dissipation of mechanical energy is unclear. To investigate this, we synthesize an actomyosin material in vitro whose active stress content can tune the network from stable to contractile. Each increment in activity determines a characteristic spectrum of actin filament fluctuations which is used to calculate the total mechanical work and the production of entropy in the material. We find that the balance of work and entropy does not increase monotonically and, surprisingly, the entropy production rate is maximized in the non-contractile, stable state. Our study provides evidence that the origins of system entropy production and activity-dependent dissipation arise from disorder in the molecular interactions between actin and myosin, Comment: 31 pages, 5 figures