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M. Lisa Manning

Publications and source records attributed to M. Lisa Manning.

51 records · Page 3Linked to original sources

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.

cond-mat.soft↗

Flocking Transition in Confluent Tissues

Collective cell migration 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. Our model reproduces the behavior observed in jammed epithelial monolayers, which are unjammed by the addition of the endocytic protein RAB5A that promotes cell motility by inducing large scale coherent migratory patterns and local fluidization.

cond-mat.soft↗

Disentangling defects and sound modes in disordered solids

We develop a new method to isolate localized defects from extended vibrational modes in disordered solids. This method augments particle interactions with an artificial potential that acts as a high-pass filter: it preserves small-scale structures while pushing extended vibrational modes to higher frequencies. The low-frequency modes that remain are "bare" defects; they are exponentially localized without the quadrupolar tails associated with elastic interactions. We demonstrate that these localized excitations are excellent predictors of plastic rearrangements in the solid. We characterize several of the properties of these defects that appear in mesoscopic theory of plasticity, including their distribution of energy barriers, number density, and size, which is a first step in testing and revising continuum models for plasticity in disordered solids.

cond-mat.soft↗

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 spatio-temporal 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.

cond-mat.soft↗

Motility-driven glass and jamming transitions in biological tissues

Cell motion inside dense tissues governs many biological processes, including embryonic development and cancer metastasis, and recent experiments suggest that these tissues exhibit collective glassy behavior. To make quantitative predictions about glass transitions in tissues, we study a self-propelled Voronoi (SPV) model that simultaneously captures polarized cell motility and multi-body cell-cell interactions in a confluent tissue, where there are no gaps between cells. We demonstrate that the model exhibits a jamming transition from a solid-like state to a fluid-like state that is controlled by three parameters: the single-cell motile speed, the persistence time of single-cell tracks, and a target shape index that characterizes the competition between cell-cell adhesion and cortical tension. In contrast to traditional particulate glasses, we are able to identify an experimentally accessible structural order parameter that specifies the entire jamming surface as a function of model parameters. We demonstrate that a continuum Soft Glassy Rheology model precisely captures this transition in the limit of small persistence times, and explain how it fails in the limit of large persistence times. These results provide a framework for understanding the collective solid-to-liquid transitions that have been observed in embryonic development and cancer progression, which may be associated with Epithelial-to-Mesenchymal transition in these tissues.

physics.bio-ph↗

A density-independent glass transition in biological tissues

Cell migration is important in many biological processes, including embryonic development, cancer metastasis, and wound healing. In these tissues, a cell's motion is often strongly constrained by its neighbors, leading to glassy dynamics. While self-propelled particle models exhibit a density-driven glass transition, this does not explain liquid-to-solid transitions in confluent tissues, where there are no gaps between cells and therefore the density is constant. Here we demonstrate the existence of a new type of rigidity transition that occurs in the well-studied vertex model for confluent tissue monolayers at constant density. We find the onset of rigidity is governed by a model parameter that encodes single-cell properties such as cell-cell adhesion and cortical tension, providing an explanation for a liquid-to-solid transitions in confluent tissues and making testable predictions about how these transitions differ from those in particulate matter.

physics.bio-ph↗

A random matrix definition of the boson peak

The density of vibrational states for glasses and jammed solids exhibits universal features, including an excess of modes above the Debye prediction known as the boson peak located at a frequency $ω^*$ . We show that the eigenvector statistics for boson peak modes are universal, and develop a new definition of the boson peak based on this universality that displays the previously observed characteristic scaling $ω^*\sim p^{-1/2}$ . We identify a large new class of random matrices that obey a generalized global tranlational invariance constraint and demonstrate that members of this class also have a boson peak with precisely the same universal eigenvector statistics. We denote this class as boson peak random matrices, and conjecture it comprises a new universality class. We characterize the eigenvector statistics as a function of coordination number, and find that one member of this new class reproduces the scaling of $ω^{*}$ with coordination number that is observed near the jamming transition.

cond-mat.soft↗

Extraction of Force-Chain Network Architecture in Granular Materials Using Community Detection

Force chains form heterogeneous physical structures that can constrain the mechanical stability and acoustic transmission of granular media. However, despite their relevance for predicting bulk properties of materials, there is no agreement on a quantitative description of force chains. Consequently, it is difficult to compare the force-chain structures in different materials or experimental conditions. To address this challenge, we treat granular materials as spatially-embedded networks in which the nodes (particles) are connected by weighted edges that represent contact forces. We use techniques from community detection, which is a type of clustering, to find sets of closely connected particles. By using a geographical null model that is constrained by the particles' contact network, we extract chain-like structures that are reminiscent of force chains. We propose three diagnostics to measure these chain-like structures, and we demonstrate the utility of these diagnostics for identifying and characterizing classes of force-chain network architectures in various materials. To illustrate our methods, we describe how force-chain architecture depends on pressure for two very different types of packings: (1) ones derived from laboratory experiments and (2) ones derived from idealized, numerically-generated frictionless packings. By resolving individual force chains, we quantify statistical properties of force-chain shape and strength, which are potentially crucial diagnostics of bulk properties (including material stability). These methods facilitate quantitative comparisons between different particulate systems, regardless of whether they are measured experimentally or numerically.

cond-mat.soft↗

Aggregation and Segregation of Confined Active Particles

We simulate a model of self-propelled disks with soft repulsive interactions confined to a box in two dimensions. For small rotational diffusion rates, monodisperse disks spontaneously accumulate at the walls. At low densities, interaction forces between particles are strongly inhomogeneous, and a simple model predicts how these inhomogeneities alter the equation of state. At higher densities, collective effects become important. We observe signatures of a jamming transition at a packing fraction $ϕ\sim 0.88$, which is also the jamming point for non-active athermal monodisperse disks. At this $ϕ$, the system develops a critical finite active speed necessary for wall aggregation. At packing fractions above $ϕ\sim 0.6$, the pressure decreases with increasing density, suggesting that strong interactions between particles are affecting the equation of state well below the jamming transition. A mixture of bidisperse disks segregates in the absence of any adhesion, identifying a new mechanism that could contribute to cell sorting in embryonic development.

cond-mat.soft↗

Energy barriers govern glassy dynamics in tissues

Recent observations demonstrate that densely packed 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 tumorigenesis.

cond-mat.soft↗

The syncytial Drosophila embryo as a mechanically excitable medium

Mitosis in the early syncytial Drosophila embryo is highly correlated in space and time, as manifested in mitotic wavefronts that propagate across the embryo. In this paper we investigate the idea that the embryo can be considered a mechanically-excitable medium, and that mitotic wavefronts can be understood as nonlinear wavefronts that propagate through this medium. We study the wavefronts via both image analysis of confocal microscopy videos and theoretical models. We find that the mitotic waves travel across the embryo at a well-defined speed that decreases with replication cycle. We find two markers of the wavefront in each cycle, corresponding to the onsets of metaphase and anaphase. Each of these onsets is followed by displacements of the nuclei that obey the same wavefront pattern. To understand the mitotic wavefronts theoretically we analyze wavefront propagation in excitable media. We study two classes of models, one with biochemical signaling and one with mechanical signaling. We find that the dependence of wavefront speed on cycle number is most naturally explained by mechanical signaling, and that the entire process suggests a scenario in which biochemical and mechanical signaling are coupled.

physics.bio-ph↗

Glassy dynamics in three-dimensional embryonic tissues

Many biological tissues are viscoelastic, behaving as elastic solids on short timescales and fluids on long timescales. This collective mechanical behavior enables and helps to guide pattern formation and tissue layering. Here we investigate the mechanical properties of three-dimensional tissue explants from zebrafish embryos by analyzing individual cell tracks and macroscopic mechanical response. We find that the cell dynamics inside the tissue exhibit features of supercooled fluids, including subdiffusive trajectories and signatures of caging behavior. We develop a minimal, three-parameter mechanical model for these dynamics, which we calibrate using only information about cell tracks. This model generates predictions about the macroscopic bulk response of the tissue (with no fit parameters) that are verified experimentally, providing a strong validation of the model. The best-fit model parameters indicate that although the tissue is fluid-like, it is close to a glass transition, suggesting that small changes to single-cell parameters could generate a significant change in the viscoelastic properties of the tissue. These results provide a robust framework for quantifying and modeling mechanically-driven pattern formation in tissues.

cond-mat.soft↗

Vibrational modes identify soft spots in a sheared disordered packing

We analyze low-frequency vibrational modes in a two-dimensional, zero-temperature, quasistatically sheared model glass to identify a population of structural "soft spots" where particle rearrangements are initiated. The population of spots evolves slowly compared to the interval between particle rearrangements and the soft spots are structurally different from the rest of the system. Our results suggest that disordered solids flow via localized rearrangements that tend to occur at soft spots, which are analogous to dislocations in crystalline solids.

cond-mat.soft↗

Descriptor approach for eliminating spurious eigenvalues in hydrodynamic equations

We describe a general framework for avoiding spurious eigenvalues -- unphysical unstable eigenvalues that often occur in hydrodynamic stability problems. In two example problems, we show that when system stability is analyzed numerically using {\em descriptor} notation, spurious eigenvalues are eliminated. Descriptor notation is a generalized eigenvalue formulation for differential-algebraic equations that explicitly retains algebraic constraints. We propose that spurious eigenvalues are likely to occur when algebraic constraints are used to analytically reduce the number of independent variables in a differential-algebraic system of equations before the system is approximated numerically. In contrast, the simple and easily generalizable descriptor framework simultaneously solves the differential equations and algebraic constraints and is well-suited to stability analysis in these systems.

physics.comp-ph↗

Shear strain localization in elastodynamic rupture simulations

We study strain localization as an enhanced velocity weakening mechanism on earthquake faults. Fault friction is modeled using Shear Transformation Zone (STZ) Theory, a microscopic physical model for non-affine rearrangements in granular fault gouge. STZ Theory is implemented in spring slider and dynamic rupture models of faults. We compare dynamic shear localization to deformation that is uniform throughout the gouge layer, and find that localized slip enhances the velocity weakening of the gouge. Localized elastodynamic ruptures have larger stress drops and higher peak slip rates than ruptures with homogeneous strain.

physics.geo-ph↗