Experimental evidence shows that there is a feedback between cell shape and cell motion. How this feedback impacts the collective behavior of dense cell monolayers remains an open question. We investigate the effect of a feedback that tends to align the cell crawling direction with cell elongation in a biological tissue model. We find that the alignment interaction promotes nematic patterns in the fluid phase that eventually undergo a non-equilibrium phase transition into a quasi-hexagonal solid. Meanwhile, highly asymmetric cells do not undergo the liquid-to-solid transition for any value of the alignment coupling. In this regime, the dynamics of cell centers and shape fluctuation show features typical of glassy systems.
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.
We investigate the two-dimensional melting of biological tissues that are modeled by deformable polymeric particles with multi-body interactions described by the Voronoi model. We identify the existence of the intermediate hexatic phase in this system, and the critical scaling of the associated solid-hexatic phase transition with the critical exponent $ uapprox0.65$ for the divergence of the correlation length. Moreover, we clarify the discontinuous nature of the hexatic-liquid phase transition in this system. These findings are achieved by directly analyzing systems spatial configurations with two generic machine learning approaches developed in this work, dubbed scanning-probe via which the possible existence of intermediate phases can be efficiently detected, and information-concealing via which the critical scaling of the correlation length in the vicinity of generic continuous phase transition can be extracted. Our work provides new physical insights into the fundamental nature of the two-dimensional melting of biological tissues, and establishes a new type of generic toolbox to investigate fundamental properties of phase transitions in various complex systems.
Recent advances in topological mechanics have revealed unusual phenomena such as topologically protected floppy modes and states of self-stress that are exponentially localized at boundaries and interfaces of mechanical networks. In this paper, we explore the topological mechanics of epithelial tissues, where the appearance of these boundary and interface modes could lead to localized soft or stressed spots and play a role in morphogenesis. We consider both a simple vertex model (VM) governed by an effective elastic energy and its generalization to an active tension network (ATN) which incorporates active adaptation of the cytoskeleton. By analyzing spatially periodic lattices at the Maxwell point of mechanical instability, we find topologically polarized phases with exponential localization of floppy modes and states of self-stress in the ATN when cells are allowed to become concave, but not in the VM.
A large class of mesoscopic or macroscopic flocking theories are coarse-grained from microscopic models that feature binary interactions as the chief aligning mechanism. However while such theories seemingly predict the existence of polar order with just binary interactions, actomyosin motility assay experiments show that binary interactions are insufficient to obtain polar order, especially at high densities. To resolve this paradox, here we introduce a solvable one-dimensional flocking model and derive its stochastic hydrodynamics. We show that two-body interactions are insufficient to generate polar order unless the noise is non-Gaussian. We show that noisy three-body interactions in the microscopic theory allow us to capture all essential dynamical features of the flocking transition, in systems that achieve orientational order above a critical density.
The present work presents a density-functional microscopic model of soft biological tissue. The model was based on a prototype molecular structure from experimentally resolved collagen peptide residues and water clusters and has the objective to capture some well-known experimental features of soft tissues. It was obtained the optimized geometry, binding and coupling energies and dipole moments. The results concerning the stability of the confined water clusters, the water-water and water-collagen interactions within the CLBM framework were successfully correlated to some important trends observed experimentally in inflammatory tissues.