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Souvik Sadhukhan

Publications and source records attributed to Souvik Sadhukhan.

9 recordsLinked to original sources

Shear effects in active models of normal and cancer cells

Mechanical properties of biological tissues, driven by passive and active forces, play a vital role in several processes ranging from development to cancer metastasis. However, the dynamical responses of cells in tissues, subject to mechanical deformations such as shear and the associated rheological properties, are not well characterized. Here, we use three-dimensional agent-based models for normal and cancer tissues to investigate their responses to simple shear as a function of cell stiffness and stochastic active forces. In the normal epithelium, with uniform strength of active force, the yield stress as a function of shear rate follows the Herschel-Bulkley form over a range of cell volume fraction. Strikingly, the shear rate dependence and the elasticity-dependent changes in the yield stress fall on master curves upon suitable scaling. To model cancer-like behavior, a certain fraction ($N_p$) of cells was chosen to have enhanced activity and decreased stiffness. As $N_p$ increases, the extent of collective cell movement decreases, transitioning from affine (collective) to non-affine (individualistic) movement, a finding that is in accord with imaging experiments. Simulations of a model of a stiff solid tumor, with radius $R_s$ embedded in normal tissue, show that as $R_s$ increases, the yield stress increases. Interestingly, the cells migrate collectively as $R_s$ increases. A Gaussian Mixture Model (GMM) and a mean field theory quantitatively account for the simulation as well as experimental results on cancerous, non-cancerous, and a mixture of these two types. The combined theoretical and experimental study establishes that heterogeneity in stiffness and activity determines non-affine movements in normal and cancer tissues.

cond-mat.soft

Fluctuation-dominated phase ordering in the one dimensional Truncated Inverse Distance Square Ising (TIDSI) model

Many physical systems, including some examples of active matter, granular assemblies, and biological systems, show fluctuation-dominated phase ordering (FDPO), where macroscopic fluctuations coexist with long-range order. Most of these systems are out of equilibrium. By contrast, a recent work has analytically demonstrated that an equilibrium one-dimensional Truncated Inverse Distance Square Ising (TIDSI) model shows FDPO. The analytical results rely on a cluster representation of the model that we term TIDSI-CL and are governed by the ratio, $c$, of the long-range interaction strength to the critical temperature. We show that the allowed range of $c$ is very narrow in the TIDSI model while it is unbounded in TIDSI-CL. We perform Monte-Carlo simulations for the TIDSI model and show consistency with the analytical results in the allowed range of $c$. The correlation length grows strongly on approaching the critical point, leading to a broad near-critical region. Within this region, $α$, which is the cusp exponent of the power-law decay of the scaled correlation function at criticality, changes to $α^\text{eff}$. We also investigate the coarsening dynamics of the model: the correlation function, domain size distribution, and aging behavior are consistent with the equilibrium properties upon replacing the system size, $L$, with the coarsening length, $\mathcal{L}(t)$. The mean largest cluster size shows logarithmic corrections due to finite $L$ and waiting time, $t_w$. The aging autocorrelation function exhibits two different scaling forms, characterized by exponents $β$ and $γ$, at short and long times compared to $t_w$, where $β=α/2$.

cond-mat.stat-mech

Growing length and time scales in activity-mediated glassy dynamics in confluent cell monolayers

Activity-mediated unjamming of a confluent glassy system is crucial for several biological processes, such as embryogenesis and cancer metastasis. During these processes, the cells progressively change their junction properties, characterized by an interaction parameter $p_0$, and become motile. Here, we study the effect of nonequilibrium active fluctuations, in the form of self-propulsion, on the glassy dynamics in a confluent system. We simulate the active Vertex model and use the analytical mode-coupling theory (MCT) to show that the nature of the transition in the presence of activity remains similar to that in a thermal system where the fluctuations are temperature-like. The agreement of the simulation results with the MCT predictions demonstrates that the structure-dynamics feedback mechanism controls the relaxation dynamics. In addition, we present the first computation of a dynamic length scale, $ξ_d$, in confluent systems using finite-size scaling, and show that the growing relaxation time exhibita a power-law dependence on $ξ_d$. Furthermore, unlike particulate glasses, the static length that governs the finite-size scaling of the relaxation time is proportional to $ξ_d$, revealing the unique nature of the glassy dynamics in confluent systems.

cond-mat.soft

Motility driven glassy dynamics in confluent epithelial monolayers

As wounds heal, embryos develop, cancer spreads, or asthma progresses, the cellular monolayer undergoes glass transition between solid-like jammed and fluid-like flowing states. During some of these processes, the cells undergo an epithelial-to-mesenchymal transition (EMT): they acquire in-plane polarity and become motile. Thus, how motility drives the glassy dynamics in epithelial systems is critical for the EMT process. However, no analytical framework that is indispensable for deeper insights exists. Here, we develop such a theory inspired by a well-known glass theory. One crucial result of this work is that the confluency affects the effective persistence time-scale of active force, described by its rotational diffusivity, $D_r^{\text{eff}}$. $D_r^{\text{eff}}$ differs from the bare rotational diffusivity, $D_r$, of the motile force due to cell shape dynamics, which acts to rectify the force dynamics: $D_r^{\text{eff}}$ is equal to $D_r$ when $D_r$ is small and saturates when $D_r$ is large. We test the theoretical prediction of $D_r^{\text{eff}}$ and how it affects the relaxation dynamics in our simulations of active Vertex model. This novel effect of $D_r^{\text{eff}}$ is crucial to understanding the new and previously published simulation data of active glassy dynamics in epithelial monolayers.

cond-mat.soft

The structure-dynamics feedback mechanism governs the glassy dynamics in epithelial monolayers

The glassy dynamics in confluent epithelial monolayers is crucial for several biological processes, such as wound healing, embryogenesis, cancer progression, etc. Several experiments have indicated that, unlike particulate systems, the glassy dynamics in these systems correlates with the static properties and shows a readily-found sub-Arrhenius relaxation. However, whether the statics-dynamics correlation is only qualitative or can provide quantitative predictions and what leads to the sub-Arrhenius relaxation remains unclear. We apply a particular analytical theory of glassy dynamics, the mode-coupling theory (MCT) that predicts dynamics using static properties alone as input, to the confluent systems. We demonstrate the remarkable applicability of MCT in simulations of the Vertex model and experiments on Madin-Darby Canine Kidney cells and show the quantitative nature of the structure-dynamics correlation in these systems. Our results elucidate that the structure-dynamics feedback mechanism of MCT, and not the barrier crossing mechanism, dominates the glassy dynamics in these systems where the relaxation time diverges as a power law with a universal exponent of $3/2$. This slower-than-exponential divergence naturally explains the sub-Arrhenius relaxation dynamics in these systems. The quantitative nature of the structure-dynamics correlation also suggests the possibility of describing various complex biological processes, such as cell division and apoptosis, via the static properties of the systems, such as cell shape or shape variability.

cond-mat.soft

A perspective on active glassy dynamics in biological systems

Dynamics is central to living systems. In the last two decades, experiments have revealed that the dynamics in diverse biological systems - from intracellular cytoplasm to cellular and organismal aggregates - are remarkably similar to that in dense systems of inanimate particles in equilibrium. They show a glass transition from a solid-like jammed state to a fluid-like flowing state, where a moderate change in control parameter leads to an enormous variation in relaxation time. However, biological systems have crucial differences from the equilibrium systems: the former have activity that drives them out of equilibrium, novel control parameters, and enormous levels of complexity. These active systems showing glassy dynamics are known as active glasses. The field is at the interface of physics and biology, freely borrowing tools from both disciplines and promising novel, fascinating discoveries. We review the experiments that started this field, simulations that have been instrumental for insights, and theories that have helped unify diverse phenomena, reveal correlations, and make novel quantitative predictions. We discuss the primary characteristics that define a glassy system. For most concepts, we first discuss the known equilibrium scenario and then present the key aspects when activity is introduced. We end the article with a discussion of the challenges in the field and possible future directions.

cond-mat.soft

A shape-driven reentrant jamming transition in confluent monolayers of synthetic cell-mimics

Many critical biological processes, like wound healing, require confluent cell monolayers/bulk tissues to transition from a jammed solid-like to a fluid-like state. Although numerical studies anticipate changes in the cell shape alone can lead to unjamming, experimental support for this prediction is not definitive because, in living systems, fluidization due to density changes cannot be ruled out. Additionally, a cell's ability to modulate its motility only compounds difficulties since even in assemblies of rigid active particles, changing the nature of self-propulsion has non-trivial effects on the dynamics. Here, we design and assemble a monolayer of synthetic cell-mimics and examine their collective behaviour. By systematically increasing the persistence time of self-propulsion, we discovered a cell shape-driven, density-independent, re-entrant jamming transition. Notably, we observed cell shape and shape variability were mutually constrained in the confluent limit and followed the same universal scaling as that observed in confluent epithelia. Dynamical heterogeneities, however, did not conform to this scaling, with the fast cells showing suppressed shape variability, which our simulations revealed is due to a transient confinement effect of these cells by their slower neighbors. Our experiments unequivocally establish a morphodynamic link, demonstrating that geometric constraints alone can dictate epithelial jamming/unjamming.

cond-mat.soft

The origin of universal cell shape variability in a confluent epithelial monolayer

Cell shape is fundamental in biology. The average cell shape can influence crucial biological functions, such as cell fate and division orientation. But cell-to-cell shape variability is often regarded as noise. In contrast, recent works reveal that shape variability in diverse epithelial monolayers follows a nearly universal distribution. However, the origin and implications of this universality are unclear. Here, assuming contractility and adhesion are crucial for cell shape, characterized via aspect ratio (AR), we develop a mean-field analytical theory for shape variability. We find that a single parameter, $α$, containing all the system-specific details, describes the probability distribution function (PDF) of AR; this leads to a universal relation between the standard deviation and the average of AR. The PDF for the scaled AR is not strictly but almost universal. The functional form is not related to jamming, contrary to common beliefs, but a consequence of a mathematical property. In addition, we obtain the scaled area distribution, described by the parameter $μ$. We show that $α$ and $μ$ together can distinguish the effects of changing physical conditions, such as maturation, on different system properties. The theory is verified in simulations of two distinct models of epithelial monolayers and agrees well with existing experiments. We demonstrate that in a confluent monolayer, average shape determines both the shape variability and dynamics. Our results imply the cell shape variability is inevitable, where a single parameter describes both statics and dynamics and provides a framework to analyze and compare diverse epithelial systems.

cond-mat.soft

Theory and simulation for equilibrium glassy dynamics in cellular Potts model of confluent biological tissue

Glassy dynamics in a confluent monolayer is indispensable in morphogenesis, wound healing, bronchial asthma, and many others; a detailed theoretical framework for such a system is, therefore, important. Vertex model (VM) simulations have provided crucial insights into the dynamics of such systems, but their nonequilibrium nature makes it difficult for theoretical development. Cellular Potts model (CPM) of confluent monolayer provides an alternative model for such systems with a well-defined equilibrium limit. We combine numerical simulations of CPM and an analytical study based on one of the most successful theories of equilibrium glass, the random first order transition theory, and develop a comprehensive theoretical framework for a confluent glassy system. We find that the glassy dynamics within CPM is qualitatively similar to that in VM. Our study elucidates the crucial role of geometric constraints in bringing about two distinct regimes in the dynamics, as the target perimeter $P_0$ is varied. The unusual sub-Arrhenius relaxation results from the distinctive interaction potential arising from the perimeter constraint in such systems. Fragility of the system decreases with increasing $P_0$ in the low-$P_0$ regime, whereas the dynamics is independent of $P_0$ in the other regime. The rigidity transition, found in VM, is absent within CPM; this difference seems to come from the nonequilibrium nature of the former. We show that CPM captures the basic phenomenology of glassy dynamics in a confluent biological system via comparison of our numerical results with existing experiments on different systems.

cond-mat.soft