Network physics of attractive colloidal gels: Resilience, rigidity, and phase diagram.

Colloidal gels exhibit solid-like behavior at vanishingly small fractions of solids, owing to ramified space-spanning networks that form due to particle-particle interactions. These networks give the gel its rigidity, and with stronger attractions the elasticity grows as well. The emergence of rigidity can be described through a mean field approach; nonetheless, fundamental understanding of how rigidity varies in gels of different attractions is lacking. Moreover, recovering an accurate gelation phase diagram based on the system's variables has been an extremely challenging task. Understanding the nature of colloidal clusters, and how rigidity emerges from their connections is key to controlling and designing gels with desirable properties. Here, we employ network analysis tools to interrogate and characterize the colloidal structures. We construct a particle-level network, having all the spatial coordinates of colloids with different attraction levels, and also identify polydisperse rigid fractal clusters using a Gaussian mixture model, to form a coarse-grained cluster network that distinctly shows main physical features of the colloidal gels. A simple mass-spring model then is used to recover quantitatively the elasticity of colloidal gels from these cluster networks. Interrogating the resilience of these gel networks shows that the elasticity of a gel (a dynamic property) is directly correlated to its cluster network's resilience (a static measure). Finally, we use the resilience investigations to devise [and experimentally validate] a fully resolved phase diagram for colloidal gelation, with a clear solid-liquid phase boundary using a single volume fraction of particles well beyond this phase boundary.

Cell Division and Motility Enable Hexatic Order in Biological Tissues.

Biological tissues transform between solid- and liquidlike states in many fundamental physiological events. Recent experimental observations further suggest that in two-dimensional epithelial tissues these solid-liquid transformations can happen via intermediate states akin to the intermediate hexatic phases observed in equilibrium two-dimensional melting. The hexatic phase is characterized by quasi-long-range (power-law) orientational order but no translational order, thus endowing some structure to an otherwise structureless fluid. While it has been shown that hexatic order in tissue models can be induced by motility and thermal fluctuations, the role of cell division and apoptosis (birth and death) has remained poorly understood, despite its fundamental biological role. Here we study the effect of cell division and apoptosis on global hexatic order within the framework of the self-propelled Voronoi model of tissue. Although cell division naively destroys order and active motility facilitates deformations, we show that their combined action drives a liquid-hexatic-liquid transformation as the motility increases. The hexatic phase is accessed by the delicate balance of dislocation defect generation from cell division and the active binding of disclination-antidisclination pairs from motility. We formulate a mean-field model to elucidate this competition between cell division and motility and the consequent development of hexatic order.

Effect of non-linear strain stiffening in eDAH and unjamming.

In cell clusters, the prominent factors at play encompass contractility-based enhanced tissue surface tension and cell unjamming transition. The former effect pertains to the boundary effect, while the latter constitutes a bulk effect. Both effects share outcomes of inducing significant elongation in cells. This elongation is so substantial that it surpasses the limits of linear elasticity, thereby giving rise to additional effects. To investigate these effects, we employ atomic force microscopy (AFM) to analyze how the mechanical properties of individual cells change under such considerable elongation. Our selection of cell lines includes MCF-10A, chosen for its pronounced demonstration of the extended differential adhesion hypothesis (eDAH), and MDA-MB-436, selected due to its manifestation of cell unjamming behavior. In the AFM analyses, we observe a common trend in both cases: as elongation increases, both cell lines exhibit strain stiffening. Notably, this effect is more prominent in MCF-10A compared to MDA-MB-436. Subsequently, we employ AFM on a dynamic range of 1-200 Hz to probe the mechanical characteristics of cell spheroids, focusing on both surface and bulk mechanics. Our findings align with the results from single cell investigations. Specifically, MCF-10A cells, characterized by strong contractile tissue tension, exhibit the greatest stiffness on their surface. Conversely, MDA-MB-436 cells, which experience significant elongation, showcase their highest stiffness within the bulk region. Consequently, the concept of single cell strain stiffening emerges as a crucial element in understanding the mechanics of multicellular spheroids (MCSs), even in the case of MDA-MB-436 cells, which are comparatively softer in nature.

Configurational fingerprints of multicellular living systems.

Cells cooperate as groups to achieve structure and function at the tissue level, during which specific material characteristics emerge. Analogous to phase transitions in classical physics, transformations in the material characteristics of multicellular assemblies are essential for a variety of vital processes including morphogenesis, wound healing, and cancer. In this work, we develop configurational fingerprints of particulate and multicellular assemblies and extract volumetric and shear order parameters based on this fingerprint to quantify the system disorder. Theoretically, these two parameters form a complete and unique pair of signatures for the structural disorder of a multicellular system. The evolution of these two order parameters offers a robust and experimentally accessible way to map the phase transitions in expanding cell monolayers and during embryogenesis and invasion of epithelial spheroids.

Nature-inspired designs for disordered acoustic bandgap materials.

We introduce an amorphous mechanical metamaterial inspired by how cells pack in biological tissues. The spatial heterogeneity in the local stiffness of these materials has been recently shown to impact the mechanics of confluent biological tissues and cancer tumor invasion. Here we use this bio-inspired structure as a design template to construct mechanical metamaterials and show that this heterogeneity can give rise to amorphous cellular solids with large, tunable acoustic bandgaps. Unlike acoustic crystals with periodic structures, the bandgaps here are directionally isotropic and robust to defects due to their complete lack of positional order. Possible ways to manipulate bandgaps are explored with a combination of the tissue-level elastic modulus and local stiffness heterogeneity of cells. To further demonstrate the existence of bandgaps, we dynamically perturb the system with an external sinusoidal wave in the perpendicular and horizontal directions. The transmission coefficients are calculated and show valleys that coincide with the location of bandgaps. Experimentally this design should lead to the engineering of self-assembled rigid acoustic structures with full bandgaps that can be controlled via mechanical tuning and promote applications in a broad area from vibration isolations to mechanical waveguides.

Bridging the gap between collective motility and epithelial-mesenchymal transitions through the active finite voronoi model.

We introduce an active version of the recently proposed finite Voronoi model of epithelial tissue. The resultant Active Finite Voronoi (AFV) model enables the study of both confluent and non-confluent geometries and transitions between them, in the presence of active cells. Our study identifies six distinct phases, characterized by aggregation-segregation, dynamical jamming-unjamming, and epithelial-mesenchymal transitions (EMT), thereby extending the behavior beyond that observed in previously studied vertex-based models. The AFV model with rich phase diagram provides a cohesive framework that unifies the well-observed progression to collective motility via unjamming with the intricate dynamics enabled by EMT. This approach should prove useful for challenges in developmental biology systems as well as the complex context of cancer metastasis. The simulation code is also provided.

Discontinuous rigidity transition associated with shear jamming in granular simulations.

We investigate the rigidity transition associated with shear jamming in frictionless, as well as frictional, disk packings in the quasi-static regime and at low shear rates. For frictionless disks, the transition under quasi-static shear is discontinuous, with an instantaneous emergence of a system spanning rigid clusters at the jamming transition. For frictional systems, the transition appears continuous for finite shear rates, but becomes sharper for lower shear rates. In the quasi-static limit, it is discontinuous as in the frictionless case. Thus, our results show that the rigidity transition associated with shear jamming is discontinuous, as demonstrated in the past for isotropic jamming of frictionless particles, and therefore a unifying feature of the jamming transition in general.

Shear-Driven Solidification and Nonlinear Elasticity in Epithelial Tissues.

Biological processes, from morphogenesis to tumor invasion, spontaneously generate shear stresses inside living tissue. The mechanisms that govern the transmission of mechanical forces in epithelia and the collective response of the tissue to bulk shear deformations remain, however, poorly understood. Using a minimal cell-based computational model, we investigate the constitutive relation of confluent tissues under simple shear deformation. We show that an initially undeformed fluidlike tissue acquires finite rigidity above a critical applied strain. This is akin to the shear-driven rigidity observed in other soft matter systems. Interestingly, shear-driven rigidity can be understood by a critical scaling analysis in the vicinity of the second order critical point that governs the liquid-solid transition of the undeformed system. We further show that a solidlike tissue responds linearly only to small strains and but then switches to a nonlinear response at larger stains, with substantial stiffening. Finally, we propose a mean-field formulation for cells under shear that offers a simple physical explanation of shear-driven rigidity and nonlinear response in a tissue.

Biological tissue-inspired tunable photonic fluid.

Inspired by how cells pack in dense biological tissues, we design 2D and 3D amorphous materials that possess a complete photonic bandgap. A physical parameter based on how cells adhere with one another and regulate their shapes can continuously tune the photonic bandgap size as well as the bulk mechanical properties of the material. The material can be tuned to go through a solid-fluid phase transition characterized by a vanishing shear modulus. Remarkably, the photonic bandgap persists in the fluid phase, giving rise to a photonic fluid that is robust to flow and rearrangements. Experimentally this design should lead to the engineering of self-assembled nonrigid photonic structures with photonic bandgaps that can be controlled in real time via mechanical and thermal tuning.

Weighting of toilet assessment scheme in China implementing analytic hierarchy process.

Advancing toilet technologies to address public health and sanitation issues are a concern of governments and organizations. This article mainly studies the assessment methods for the public toilets and some rural toilets considering from design to demolition to assist for the innovation of toilet technologies. The Analytic Hierarchy Process (AHP) and Life Cycle Assessment (LCA) methods were adopted to identify the assessment indicators and rank the weight. The outcome of Toilet Assessment Scheme (TAS), which includes a set of weightings and a classification system for the selected assessment indicators and sub-indicators. The weight calculation result showed that water resources, ecology, and indoor environmental quality are relatively high, which indicates that saving water, protecting the environment and optimizing the toilet environment should be given priority at the current stage. The individual questionnaire experts from the perspective of gender, profession, and generation, have different emphases on the evaluation scheme. This study can improve the comprehensiveness of toilet evaluation under the distinct background conditions, and will play a relevant role in the promotion of new toilet technology. The TAS can accelerate the toilet revolution in areas where toilets are scarce, and thus will improve the sanitary and health conditions of these populations.

Unjamming and collective migration in MCF10A breast cancer cell lines.

Each cell comprising an intact, healthy, confluent epithelial layer ordinarily remains sedentary, firmly adherent to and caged by its neighbors, and thus defines an elemental constituent of a solid-like cellular collective [1,2]. After malignant transformation, however, the cellular collective can become fluid-like and migratory, as evidenced by collective motions that arise in characteristic swirls, strands, ducts, sheets, or clusters [3,4]. To transition from a solid-like to a fluid-like phase and thereafter to migrate collectively, it has been recently argued that cells comprising the disordered but confluent epithelial collective can undergo changes of cell shape so as to overcome geometric constraints attributable to the newly discovered phenomenon of cell jamming and the associated unjamming transition (UJT) [1,2,5-9]. Relevance of the jamming concept to carcinoma cells lines of graded degrees of invasive potential has never been investigated, however. Using classical in vitro cultures of six breast cancer model systems, here we investigate structural and dynamical signatures of cell jamming, and the relationship between them [1,2,10,11]. In order of roughly increasing invasive potential as previously reported, model systems examined included MCF10A, MCF10A.Vector; MCF10A.14-3-3ζ; MCF10.ErbB2, MCF10AT; and MCF10CA1a [12-15]. Migratory speed depended on the particular cell line. Unsurprisingly, for example, the MCF10CA1a cell line exhibited much faster migratory speed relative to the others. But unexpectedly, across different cell lines higher speeds were associated with enhanced size of cooperative cell packs in a manner reminiscent of a peloton [9]. Nevertheless, within each of the cell lines evaluated, cell shape and shape variability from cell-to-cell conformed with predicted structural signatures of cell layer unjamming [1]. Moreover, both structure and migratory dynamics were compatible with previous theoretical descriptions of the cell jamming mechanism [2,10,11,16,17]. As such, these findings demonstrate the richness of the cell jamming mechanism, which is now seen to apply across these cancer cell lines but remains poorly understood.

Correlating cell shape and cellular stress in motile confluent tissues.

Collective cell migration is a highly regulated process involved in wound healing, cancer metastasis, and morphogenesis. Mechanical interactions among cells provide an important regulatory mechanism to coordinate such collective motion. Using a self-propelled Voronoi (SPV) model that links cell mechanics to cell shape and cell motility, we formulate a generalized mechanical inference method to obtain the spatiotemporal distribution of cellular stresses from measured traction forces in motile tissues and show that such traction-based stresses match those calculated from instantaneous cell shapes. We additionally use stress information to characterize the rheological properties of the tissue. We identify a motility-induced swim stress that adds to the interaction stress to determine the global contractility or extensibility of epithelia. We further show that the temporal correlation of the interaction shear stress determines an effective viscosity of the tissue that diverges at the liquid-solid transition, suggesting the possibility of extracting rheological information directly from traction data.

Mechanical Heterogeneity in Tissues Promotes Rigidity and Controls Cellular Invasion.

We study the influence of cell-level mechanical heterogeneity in epithelial tissues using a vertex-based model. Heterogeneity is introduced into the cell shape index (p_{0}) that tunes the stiffness at a single-cell level. The addition of heterogeneity can always enhance the mechanical rigidity of the epithelial layer by increasing its shear modulus, hence making it more rigid. There is an excellent scaling collapse of our data as a function of a single scaling variable f_{r}, which accounts for the overall fraction of rigid cells. We identify a universal threshold f_{r}^{*} that demarcates fluid versus solid tissues. Furthermore, this rigidity onset is far below the contact percolation threshold of rigid cells. These results give rise to a separation of rigidity and contact percolation processes that leads to distinct types of solid states. We also investigate the influence of heterogeneity on tumor invasion dynamics. There is an overall impedance of invasion as the tissue becomes more rigid. Invasion can also occur in an intermediate heterogeneous solid state that is characterized by significant spatial-temporal intermittency.

Cooperation of dual modes of cell motility promotes epithelial stress relaxation to accelerate wound healing.

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.

Hydrodynamics of shape-driven rigidity transitions in motile tissues.

In biological tissues, it is now well-understood that mechanical cues are a powerful mechanism for pattern regulation. While much work has focused on interactions between cells and external substrates, recent experiments suggest that cell polarization and motility might be governed by the internal shear stiffness of nearby tissue, deemed "plithotaxis". Meanwhile, other work has demonstrated that there is a direct relationship between cell shapes and tissue shear modulus in confluent tissues. Joining these two ideas, we develop a hydrodynamic model that couples cell shape, and therefore tissue stiffness, to cell motility and polarization. Using linear stability analysis and numerical simulations, we find that tissue behavior can be tuned between largely homogeneous states and patterned states such as asters, controlled by a composite "morphotaxis" parameter that encapsulates the nature of the coupling between shape and polarization. The control parameter is in principle experimentally accessible, and depends both on whether a cell tends to move in the direction of lower or higher shear modulus, and whether sinks or sources of polarization tend to fluidize the system.

Flocking transitions in confluent tissues.

Collective cell migration in dense tissues underlies important biological processes, such as embryonic development, wound healing and cancer invasion. While many aspects of single cell movements are now well established, the mechanisms leading to displacements of cohesive cell groups are still poorly understood. To elucidate the emergence of collective migration in mechanosensitive cells, we examine a self-propelled Voronoi (SPV) model of confluent tissues with an orientational feedback that aligns a cell's polarization with its local migration velocity. While shape and motility are known to regulate a density-independent liquid-solid transition in tissues, we find that aligning interactions facilitate collective motion and promote solidification, with transitions that can be predicted by extending statistical physics tools such as effective temperature to this far-from-equilibrium system. In addition to accounting for recent experimental observations obtained with epithelial monolayers, our model predicts structural and dynamical signatures of flocking, which may serve as gateway to a more quantitative characterization of collective motility.

Jamming by shear.

A broad class of disordered materials including foams, glassy molecular systems, colloids and granular materials can form jammed states. A jammed system can resist small stresses without deforming irreversibly, whereas unjammed systems flow under any applied stresses. The broad applicability of the Liu-Nagel jamming concept has attracted intensive theoretical and modelling interest but has prompted less experimental effort. In the Liu-Nagel framework, jammed states of athermal systems exist only above a certain critical density. Although numerical simulations for particles that do not experience friction broadly support this idea, the nature of the jamming transition for frictional grains is less clear. Here we show that jamming of frictional, disk-shaped grains can be induced by the application of shear stress at densities lower than the critical value, at which isotropic (shear-free) jamming occurs. These jammed states have a much richer phenomenology than the isotropic jammed states: for small applied shear stresses, the states are fragile, with a strong force network that percolates only in one direction. A minimum shear stress is needed to create robust, shear-jammed states with a strong force network percolating in all directions. The transitions from unjammed to fragile states and from fragile to shear-jammed states are controlled by the fraction of force-bearing grains. The fractions at which these transitions occur are statistically independent of the density. Jammed states with densities lower than the critical value have an anisotropic fabric (contact network). The minimum anisotropy of shear-jammed states vanishes as the density approaches the critical value from below, in a manner reminiscent of an order-disorder transition.

Unjamming and cell shape in the asthmatic airway epithelium.

From coffee beans flowing in a chute to cells remodelling in a living tissue, a wide variety of close-packed collective systems-both inert and living-have the potential to jam. The collective can sometimes flow like a fluid or jam and rigidify like a solid. The unjammed-to-jammed transition remains poorly understood, however, and structural properties characterizing these phases remain unknown. Using primary human bronchial epithelial cells, we show that the jamming transition in asthma is linked to cell shape, thus establishing in that system a structural criterion for cell jamming. Surprisingly, the collapse of critical scaling predicts a counter-intuitive relationship between jamming, cell shape and cell-cell adhesive stresses that is borne out by direct experimental observations. Cell shape thus provides a rigorous structural signature for classification and investigation of bronchial epithelial layer jamming in asthma, and potentially in any process in disease or development in which epithelial dynamics play a prominent role.

Energy barriers and cell migration in densely packed tissues.

Recent observations demonstrate that confluent tissues exhibit features of glassy dynamics, such as caging behavior and dynamical heterogeneities, although it has remained unclear how single-cell properties control this behavior. Here we develop numerical and theoretical models to calculate energy barriers to cell rearrangements, which help govern cell migration in cell monolayers. In contrast to work on sheared foams, we find that energy barrier heights are exponentially distributed and depend systematically on the cell's number of neighbors. Based on these results, we predict glassy two-time correlation functions for cell motion, with a timescale that increases rapidly as cell activity decreases. These correlation functions are used to construct simple random walks that reproduce the caging behavior observed for cell trajectories in experiments. This work provides a theoretical framework for predicting collective motion of cells in wound-healing, embryogenesis and cancer tumorogenesis.

Regulation of Chromatin Modifications through Coordination of Nucleus Size and Epithelial Cell Morphology Heterogeneity.

Cell morphology heterogeneity within epithelial collectives is a pervasive phenomenon intertwined with tissue mechanical properties. Despite its widespread occurrence, the underlying mechanisms driving cell morphology heterogeneity and its consequential biological ramifications remain elusive. Here, we investigate the dynamic evolution of epithelial cell morphology and nucleus morphology during crowding, unveiling a consistent correlation between the two. Our investigation reveals a persistent log-normal probability distribution characterizing both cell and nucleus areas across diverse crowding stages and epithelial model systems. We showed that this morphological diversity arises from asymmetric partitioning during cell division and is perpetuated through actomyosin-mediated regulation of cell-nucleus size coordination. Moreover, we provide insights into the impact of nucleus morphology on chromatin dynamics, demonstrating that constraining nucleus area leads to downregulation of the euchromatic mark H3K9ac and upregulation of the heterochromatic mark H3K27me3 through modulation of histone demethylase UTX expression. These findings under-score the significance of cell morphology heterogeneity as a driver of chromatin state diversity, shaping functional variability within epithelial tissues.