Cell cycle-dependent active stress drives epithelia remodeling.

Epithelia have distinct cellular architectures which are established in development, reestablished after wounding, and maintained during tissue homeostasis despite cell turnover and mechanical perturbations. In turn, cell shape also controls tissue function as a regulator of cell differentiation, proliferation, and motility. Here, we investigate cell shape changes in a model epithelial monolayer. After the onset of confluence, cells continue to proliferate and change shape over time, eventually leading to a final architecture characterized by arrested motion and more regular cell shapes. Such monolayer remodeling is robust, with qualitatively similar evolution in cell shape and dynamics observed across disparate perturbations. Here, we quantify differences in monolayer remodeling guided by the active vertex model to identify underlying order parameters controlling epithelial architecture. When monolayers are formed atop an extracellular matrix with varied stiffness, we find the cell density at which motion arrests varies significantly, but the cell shape remains constant, consistent with the onset of tissue rigidity. In contrast, pharmacological perturbations can significantly alter the cell shape at which tissue dynamics are arrested, consistent with varied amounts of active stress within the tissue. Across all experimental conditions, the final cell shape is well correlated to the cell proliferation rate, and cell cycle inhibition immediately arrests cell motility. Finally, we demonstrate cell cycle variation in junctional tension as a source of active stress within the monolayer. Thus, the architecture and mechanics of epithelial tissue can arise from an interplay between cell mechanics and stresses arising from cell cycle dynamics.

Non-monotonic fluidization generated by fluctuating edge tensions in confluent tissues.

In development and homeostasis, multi-cellular systems exhibit spatial and temporal heterogeneity in their biochemical and mechanical properties. Nevertheless, it remains unclear how spatiotemporally heterogeneous forces affect the dynamical and mechanical properties of confluent tissue. To address this question, we study the dynamical behavior of the two-dimensional cellular vertex model for epithelial monolayers in the presence of fluctuating cell-cell interfacial tensions, which is a biologically relevant source of mechanical spatiotemporal heterogeneity. In particular, we investigate the effects of the amplitude and persistence time of fluctuating tension on the tissue dynamics. We unexpectedly find that the long-time diffusion constant describing cell rearrangements depends non-monotonically on the persistence time, while it increases monotonically as the amplitude increases. Our analysis indicates that at low and intermediate persistence times tension fluctuations drive motion of vertices and promote cell rearrangements, while at the highest persistence times the tension in the network evolves so slowly that rearrangements become rare.

Quantifying the link between local structure and cellular rearrangements using information in models of biological tissues.

Machine learning techniques have been used to quantify the relationship between local structural features and variations in local dynamical activity in disordered glass-forming materials. To date these methods have been applied to an array of standard (Arrhenius and super-Arrhenius) glass formers, where work on "soft spots" indicates a connection between the linear vibrational response of a configuration and the energy barriers to non-linear deformations. Here we study the Voronoi model, which takes its inspiration from dense epithelial monolayers and which displays anomalous, sub-Arrhenius scaling of its dynamical relaxation time with decreasing temperature. Despite these differences, we find that the likelihood of rearrangements can nevertheless vary by several orders of magnitude within the model tissue and extract a local structural quantity, "softness," that accurately predicts the temperature dependence of the relaxation time. We use an information-theoretic measure to quantify the extent to which softness determines impending topological rearrangements; we find that softness captures nearly all of the information about rearrangements that is obtainable from structure, and that this information is large in the solid phase of the model and decreases rapidly as state variables are varied into the fluid phase.

Small-scale demixing in confluent biological tissues.

Surface tension governed by differential adhesion can drive fluid particle mixtures to sort into separate regions, i.e., demix. Does the same phenomenon occur in confluent biological tissues? We begin to answer this question for epithelial monolayers with a combination of theory via a vertex model and experiments on keratinocyte monolayers. Vertex models are distinct from particle models in that the interactions between the cells are shape-based, as opposed to distance-dependent. We investigate whether a disparity in cell shape or size alone is sufficient to drive demixing in bidisperse vertex model fluid mixtures. Surprisingly, we observe that both types of bidisperse systems robustly mix on large lengthscales. On the other hand, shape disparity generates slight demixing over a few cell diameters, a phenomenon we term micro-demixing. This result can be understood by examining the differential energy barriers for neighbor exchanges (T1 transitions). Experiments with mixtures of wild-type and E-cadherin-deficient keratinocytes on a substrate are consistent with the predicted phenomenon of micro-demixing, which biology may exploit to create subtle patterning. The robustness of mixing at large scales, however, suggests that despite some differences in cell shape and size, progenitor cells can readily mix throughout a developing tissue until acquiring means of recognizing cells of different types.

Disconnecting structure and dynamics in glassy thin films.

Nanometrically thin glassy films depart strikingly from the behavior of their bulk counterparts. We investigate whether the dynamical differences between a bulk and thin film polymeric glass former can be understood by differences in local microscopic structure. Machine learning methods have shown that local structure can serve as the foundation for successful, predictive models of particle rearrangement dynamics in bulk systems. By contrast, in thin glassy films, we find that particles at the center of the film and those near the surface are structurally indistinguishable despite exhibiting very different dynamics. Next, we show that structure-independent processes, already present in bulk systems and demonstrably different from simple facilitated dynamics, are crucial for understanding glassy dynamics in thin films. Our analysis suggests a picture of glassy dynamics in which two dynamical processes coexist, with relative strengths that depend on the distance from an interface. One of these processes depends on local structure and is unchanged throughout most of the film, while the other is purely Arrhenius, does not depend on local structure, and is strongly enhanced near the free surface of a film.

Glassy dynamics in models of confluent tissue with mitosis and apoptosis.

Recent work on particle-based models of tissues has suggested that any finite rate of cell division and cell death is sufficient to fluidize an epithelial tissue. At the same time, experimental evidence has indicated the existence of glassy dynamics in some epithelial layers despite continued cell cycling. To address this discrepancy, we quantify the role of cell birth and death on glassy states in confluent tissues using simulations of an active vertex model that includes cell motility, cell division, and cell death. Our simulation data is consistent with a simple ansatz in which the rate of cell-life cycling and the rate of relaxation of the tissue in the absence of cell cycling contribute independently and additively to the overall rate of cell motion. Specifically, we find that a glass-like regime with caging behavior indicated by subdiffusive cell displacements can be achieved in systems with sufficiently low rates of cell cycling.

Soft yet Sharp Interfaces in a Vertex Model of Confluent Tissue.

How can dense biological tissue maintain sharp boundaries between coexisting cell populations? We explore this question within a simple vertex model for cells, focusing on the role of topology and tissue surface tension. We show that the ability of cells to independently regulate adhesivity and tension, together with neighbor-based interaction rules, lets them support strikingly unusual interfaces. In particular, we show that mechanical- and fluctuation-based measurements of the effective surface tension of a cellular aggregate yield different results, leading to mechanically soft interfaces that are nevertheless extremely sharp.

No unjamming transition in a Voronoi model of biological tissue.

Vertex models are a popular approach to simulating the mechanical and dynamical properties of dense biological tissues, describing the tissue as a network of polygons. Recently a class of two-dimensional vertex models was shown to exhibit a disordered rigidity transition controlled by the preferred cellular geometry, which was subsequently echoed by experimental findings. An attractive variant of these models uses a Voronoi tessellation to describe the cells, which reduces the number of degrees of freedom as compared the original vertex model. The Voronoi model was also endowed with a non-equilibrium model of cellular motility, leading to rich, glassy behavior. This glassy behavior was suggested to be inextricably linked to an underlying jamming transition. We test this conjecture, exploring the low-effective-temperature limit of the 2D Voronoi model by studying cell trajectories from detailed dynamical simulations in combination with rigidity measurements of energy-minimized disordered cell configurations. We find that the zero-temperature limit of this model has no unjamming transition. We show that this absence of an unjamming transition is intimately linked to the marginality of the model, i.e. the fact that the constraints imposed on cell areas and perimeters precisely balance the number of degrees of freedom in the model. Our work suggests that constraint counting arguments are useful to understand rigidity in a broad class of models of dense biological tissues.

Curvature-dependent tension and tangential flows at the interface of motility-induced phases.

Purely repulsive active particles spontaneously undergo motility-induced phase separation (MIPS) into condensed and dilute phases. Remarkably, the mechanical tension measured along the interface between these phases is negative. In equilibrium this would imply an unstable interface that wants to expand, but these out-of-equilibrium systems display long-time stability and have intrinsically stiff boundaries. Here, we study this phenomenon in detail using active Brownian particle simulations and a novel frame of reference. By shifting from the global (or laboratory) frame to a local frame that follows the dynamics of the phase boundary, we observe correlations between the local curvature of the interface and the measured value of the tension. Importantly, our analysis reveals that curvature drives sustained local tangential motion of particles within a surface layer in both the gas and the dense regions. The combined tangential current in the gas and local "self-shearing" of the surface of the dense phase suggest a stiffening interface that redirects particles along itself to heal local fluctuations. These currents restore the otherwise wildly fluctuating interface through an out-of-equilibrium Marangoni effect. We discuss the implications of our observations on phenomenological models of interfacial dynamics.

Algorithmic lattice kirigami: A route to pluripotent materials.

We use a regular arrangement of kirigami elements to demonstrate an inverse design paradigm for folding a flat surface into complex target configurations. We first present a scheme using arrays of disclination defect pairs on the dual to the honeycomb lattice; by arranging these defect pairs properly with respect to each other and choosing an appropriate fold pattern a target stepped surface can be designed. We then present a more general method that specifies a fixed lattice of kirigami cuts to be performed on a flat sheet. This single pluripotent lattice of cuts permits a wide variety of target surfaces to be programmed into the sheet by varying the folding directions.

Reply to the 'Comment on "Spatial structure of states of self stress in jammed systems"' by E. Lerner, Soft Matter, 2017, 13, DOI.

Lerner's theoretical analysis neglects a normalizing factor which distinguishes states of self stress from the stress response to a unit dipolar force along a bond. This factor leads to different spatial profiles upon ensemble averaging.

Spatial structure of states of self stress in jammed systems.

States of self stress, organizations of internal forces in many-body systems that are in equilibrium with an absence of external forces, can be thought of as the constitutive building blocks of the elastic response of a material. In overconstrained disordered packings they have a natural mathematical correspondence with the zero-energy vibrational modes in underconstrained systems. While substantial attention in the literature has been paid to diverging length scales associated with zero- and finite-energy vibrational modes in jammed systems, less is known about the spatial structure of the states of self stress. In this work we define a natural way in which a unique state of self stress can be associated with each bond in a disordered spring network derived from a jammed packing, and then investigate the spatial structure of these bond-localized states of self stress. This allows for an understanding of how the elastic properties of a system would change upon changing the strength or even existence of any bond in the system.

Topological boundary modes in jammed matter.

Granular matter at the jamming transition is poised on the brink of mechanical stability, and hence it is possible that these random systems have topologically protected surface phonons. Studying two model systems for jammed matter, we find states that exhibit distinct mechanical topological classes, protected surface modes, and ubiquitous Weyl points. The detailed statistics of the boundary modes shed surprising light on the properties of the jamming critical point and help inform a common theoretical description of the detailed features of the transition.

A force-level theory of the rheology of entangled rod and chain polymer liquids. I. Tube deformation, microscopic yielding, and the nonlinear elastic limit.

We employ a first-principles-based, force-level approach to construct the anharmonic tube confinement field for entangled fluids of rigid needles, and also for chains described at the primitive-path (PP) level in two limiting situations where chain stretch is assumed to either be completely equilibrated or unrelaxed. The influence of shear and extensional deformation and polymer orientation is determined in a nonlinear elastic limit where dissipative relaxation processes are intentionally neglected. For needles and PP-level chains, a self-consistent analysis of transverse polymer harmonic dynamical fluctuations predicts that deformation-induced orientation leads to tube weakening or widening. In contrast, for deformed polymers in which chain stretch does not relax, we find tube strengthening or compression. For all three systems, a finite maximum transverse entanglement force localizing the polymers in effective tubes is predicted. The conditions when this entanglement force can be overcome by an externally applied force associated with macroscopic deformation can be crisply defined in the nonlinear elastic limit, and the possibility of a "microscopic absolute yielding" event destroying the tube confinement can be analyzed. For needles and contour-relaxed PP chains, this force imbalance occurs at a stress of order the equilibrium shear modulus and a strain of order unity, corresponding to a mechanically fragile entanglement tube field. However, for unrelaxed stretched chains, tube compression stabilizes transverse polymer confinement, and there appears to be no force imbalance. These results collectively suggest that the crossover from elastic to irreversible viscous response requires chain retraction to initiate disentanglement. We qualitatively discuss comparisons with existing phenomenological models for nonlinear startup shear, step strain, and creep rheology experiments.

Disordered surface vibrations in jammed sphere packings.

We study the vibrational properties near a free surface of disordered spring networks derived from jammed sphere packings. In bulk systems, without surfaces, it is well understood that such systems have a plateau in the density of vibrational modes extending down to a frequency scale ω*. This frequency is controlled by ΔZ = 〈Z〉 - 2d, the difference between the average coordination of the spheres and twice the spatial dimension, d, of the system, which vanishes at the jamming transition. In the presence of a free surface we find that there is a density of disordered vibrational modes associated with the surface that extends far below ω*. The total number of these low-frequency surface modes is controlled by ΔZ, and the profile of their decay into the bulk has two characteristic length scales, which diverge as ΔZ(-1/2) and ΔZ(-1) as the jamming transition is approached.

Making the cut: lattice kirigami rules.

In this Letter we explore and develop a simple set of rules that apply to cutting, pasting, and folding honeycomb lattices. We consider origami-like structures that are extrinsically flat away from zero-dimensional sources of Gaussian curvature and one-dimensional sources of mean curvature, and our cutting and pasting rules maintain the intrinsic bond lengths on both the lattice and its dual lattice. We find that a small set of rules is allowed providing a framework for exploring and building kirigami­folding, cutting, and pasting the edges of paper.

Self-organized vortex phases and hydrodynamic interactions in Bos taurus sperm cells.

Flocking behavior is observed in biological systems from the cellular to superorganismal length scales, and the mechanisms and purposes of this behavior are objects of intense interest. In this paper, we study the collective dynamics of bovine sperm cells in a viscoelastic fluid. These cells appear not to spontaneously flock, but transition into a long-lived flocking phase after being exposed to a transient ordering pulse of fluid flow. Surprisingly, this induced flocking phase has many qualitative similarities with the spontaneous polar flocking phases predicted by Toner-Tu theory, such as anisotropic giant number fluctuations and nontrivial transverse density correlations, despite the induced nature of the phase and the clearly important role of momentum conservation between the swimmers and the surrounding fluid in these experiments. We also find a self-organized global vortex state of the sperm cells, and map out an experimental phase diagram of states of collective motion as a function of cell density and motility statistics. We compare our experiments with a parameter-matched computational model of persistently turning active particles and find that the experimental order-disorder phase boundary as a function of cell density and persistence time can be approximately predicted from measures of single-cell properties. Our results may have implications for the evaluation of sample fertility by studying the collective phase behavior of dense groups of swimming sperm.

Entangled polymer chain melts: orientation and deformation dependent tube confinement and interchain entanglement elasticity.

The phenomenological reptation-tube model is based on a single chain perspective and was originally proposed to explain the remarkable viscoelastic properties of dense entangled polymer liquids. However, simulations over the last two decades have revealed a fundamental tension in the model: it assumes that bonded, single-chain backbone stresses are the sole polymer contribution to the slowly relaxing component of stress storage and elasticity, but mounting evidence suggests that at the local level of forces it is interchain contributions that dominate, as in simple liquids. Here we show that based on a chain model constructed at the level of self-consistently determined primitive paths, an explicit force-level treatment of the correlated intermolecular contributions to stress that arise from chain uncrossability can essentially quantitatively predict the entanglement plateau modulus associated with the soft rubbery response of polymer liquids. Analogies to transient localization and elasticity in glass-forming liquids are identified. Predictions for the effect of macroscopic deformation and anisotropic orientational order on the tube diameter are also made. Based on the interchain stress perspective the theory reproduces some aspects of the rheological response to shear and extensional deformations associated with the single chain tube model.

Effects of polydispersity on the plastic behaviors of dense two-dimensional granular systems under shear.

We study particle-scale motion in sheared highly polydisperse amorphous materials, in which the largest particles are as much as ten times the size of the smallest. We find strikingly different behavior from the more commonly studied amorphous systems with low polydispersity. In particular, an analysis of the nonaffine motion of particles reveals qualitative differences between large and small particles: The smaller particles have dramatically more nonaffine motion, which is induced by the presence of the large particles. We characterize how the nonaffine motion changes from the low- to high-polydispersity regimes. We further demonstrate a quantitative way to distinguish between "large" and "small" particles in systems with broad distributions of particle sizes. A macroscopic consequence of the nonaffine motion is a decrease in the energy dissipation rate for highly polydisperse samples, which is due both to a geometric consequence of the changing jamming conditions for higher polydispersity and to the changing character of nonaffine motion.

Microscopic theory of entangled polymer melt dynamics: flexible chains as primitive-path random walks and supercoarse grained needles.

We qualitatively extend a microscopic dynamical theory for the transverse confinement of infinitely thin rigid rods to study topologically entangled melts of flexible polymer chains. Our main result treats coils as ideal random walks of self-consistently determined primitive-path (PP) steps and exactly includes chain uncrossability at the binary collision level. A strongly anharmonic confinement potential ("tube") for a primitive path is derived and favorably compared with simulation results. The relationship of the PP-level theory to two simpler models, the melt as a disconnected fluid of primitive-path steps and a "supercoarse graining" that replaces the entire chain by a needle corresponding to its end-to-end vector, is examined. Remarkable connections between the different levels of coarse graining are established.