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Register a new userFluidization of epithelial sheets by active cell rearrangements
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We theoretically explore fluidization of epithelial tissues by active T1 neighbor exchanges. We show that the geometry of cell-cell junctions encodes important information about the local features of the energy landscape, which we support by an elastic theory of T1 transformations. Using a 3D vertex model, we show that the degree of active noise driving forced cell rearrangements governs the stress-relaxation time-scale of the tissue. We study tissue response to in-plane shear at different time scales. At short time, the tissue behaves as a solid, whereas its long-time fluid behavior can be associated with an effective viscosity which scales with the rate of active T1 transformations. Furthermore, we develop a coarse-grained theory, where we treat the tissue as an active fluid and confirm the results of the vertex model. The impact of cell rearrangements on tissue shape is illustrated by studying axial compression of an epithelial tube.
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We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies.
We show that a viscoelastic thin sheet driven out of equilibrium by active structural remodelling develops a rich variety of shapes as a result of a competition between viscous relaxation and activity. In the regime where active processes are faster than viscoelastic relaxation, wrinkles that are formed due to remodelling are unable to relax to a configuration that minimises the elastic energy and the sheet is inherently out of equilibrium. We argue that this non-equilibrium regime is of particular interest in biology as it allows the system to access morphologies that are unavailable if restricted to the adiabatic evolution between configurations that minimise the elastic energy alone. Here, we introduce activity using the formalism of evolving target metric and showcase the diversity of wrinkling morphologies arising from out of equilibrium dynamics.
The motion of soft-glassy materials (SGM) in a confined geometry is strongly impacted by surface roughness. However, the effect of the spatial distribution of the roughness remains poorly understood from a more quantitative viewpoint. Here we present a comprehensive study of concentrated emulsions flowing in microfluidic channels, one wall of which is patterned with micron-size equally spaced grooves oriented perpendicularly to the flow direction. We show that roughness-induced fluidization can be quantitatively tailored by systematically changing both the width and separation of the grooves. We find that a simple scaling law describes such fluidization as a function of the density of grooves, suggesting common scenarios for droplet trapping and release. Numerical simulations confirm these views and are used to elucidate the relation between fluidization and the rate of plastic rearrangements.
Collective cell migration is crucial in many biological processes such as wound healing, tissue morphogenesis, and tumor progression. The leading front of a collective migrating epithelial cell layer often destabilizes into multicellular finger-like protrusions, each of which is guided by a leader cell at the fingertip. Here, we develop a subcellular-element-based model of this fingering instability, which incorporates leader cells and other related properties of a monolayer of epithelial cells. Our model recovers multiple aspects of the dynamics, especially the traction force patterns and velocity fields, observed in experiments on MDCK cells. Our model predicts the necessity of the leader cell and its minimal functions for the formation and maintenance of a stable finger pattern. Meanwhile, our model allows for an analysis of the role of supra-cellular actin cable on the leading front, predicting that while this observed structure helps maintain the shape of the finger, it is not required in order to form a finger. In addition, we also study the driving instability in the context of continuum active fluid model, which justifies some of our assumptions in the computational approach. In particular, we show that in our model no finger protrusions would emerge in a phenotypically homogenous active fluid and hence the role of the leader cell and its followers are often critical.
We image local structural rearrangements in soft colloidal glasses under small periodic perturbations induced by thermal cycling. Local structural entropy $S_{2}$ positively correlates with observed rearrangements in colloidal glasses. The high $S_{2}$ values of the rearranging clusters in glasses indicate that fragile regions in glasses are structurally less correlated, similar to structural defects in crystalline solids. Slow-evolving high $S_{2}$ spots are capable of predicting local rearrangements long before the relaxations occur, while fluctuation-created high $S_{2}$ spots best correlate with local deformations right before the rearrangement events. Local free volumes are also found to correlate with particle rearrangements at extreme values, although the ability to identify relaxation sites is substantially lower than $S_{2}$. Our experiments provide an efficient structural identifier for the fragile regions in glasses, and highlight the important role of structural correlations in the physics of glasses.
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