Stress-shape misalignment in confluent cell layers.
Abstract:
In tissue formation and repair, the epithelium undergoes complex patterns of motion driven by the active forces produced by each cell. Although the principles governing how the forces evolve in time are not yet clear, it is often assumed that the contractile stresses within the cell layer align with the axis defined by the body of each cell. Here, we simultaneously measured the orientations of the cell shape and the cell-generated contractile stresses, observing correlated, dynamic domains in which the stresses were systematically misaligned with the cell body. We developed a continuum model that decouples the orientations of contractile stress and cell body. The model recovered the spatial and temporal dynamics of the regions of misalignment in the experiments. These findings reveal that the cell controls its contractile forces independently from its shape, suggesting that the physical rules relating cell forces and cell shape are more flexible than previously thought.Cell sorting by active forces in a phase-field model of cell monolayers
Abstract:
Cell sorting, the segregation of cells with different properties into distinct domains, is a key phenomenon in biological processes such as embryogenesis. We use a phase-field model of a confluent cell layer to study the role of activity in cell sorting. We find that a mixture of cells with extensile or contractile dipolar activity, and which are identical apart from their activity, quickly sort into small, elongated patches which then grow slowly in time. We interpret the sorting as driven by the different diffusivity of the extensile and contractile cells, mirroring the ordering of Brownian particles connected to different hot and cold thermostats. We check that the free energy is not changed by either partial or complete sorting, thus confirming that activity can be responsible for the ordering even in the absence of thermodynamic mechanisms.Activity-driven tissue alignment in proliferating spheroids
Abstract:
We extend the continuum theory of active nematic fluids to study cell flows and tissue dynamics inside multicellular spheroids, spherical, self-assembled aggregates of cells that are widely used as model systems to study tumour dynamics. Cells near the surface of spheroids have better access to nutrients and therefore proliferate more rapidly than those in the resource-depleted core. Using both analytical arguments and three-dimensional simulations, we find that the proliferation gradients result in flows and in gradients of activity both of which can align the orientation axis of cells inside the aggregates. Depending on environmental conditions and the intrinsic tissue properties, we identify three distinct alignment regimes: spheroids in which all the cells align either radially or tangentially to the surface throughout the aggregate and spheroids with angular cell orientation close to the surface and radial alignment in the core. The continuum description of tissue dynamics inside spheroids not only allows us to infer dynamic cell parameters from experimentally measured cell alignment profiles, but more generally motivates novel mechanisms for controlling the alignment of cells within aggregates which has been shown to influence the mechanical properties and invasive capabilities of tumors.
Viscoelastic confinement induces periodic flow reversals in active nematics
Abstract:
We use linear stability analysis and hybrid lattice Boltzmann simulations to study the dynamical behavior of an active nematic confined in a channel made of viscoelastic material. We find that the quiescent, ordered active nematic is unstable above a critical activity. The transition is to a steady flow state for high elasticity of the channel surroundings. However, below a threshold elastic modulus, the system produces spontaneous oscillations with periodic flow reversals. We provide a phase diagram that highlights the region where time-periodic oscillations are observed and explain how they are produced by the interplay of activity and viscoelasticity. Our results suggest experiments to study the role of viscoelastic confinement in the spatiotemporal organization and control of active matter.Spontaneous rotation of active droplets in two and three dimensions
Abstract:
We use numerical simulations and linear stability analysis to study active nematic droplets in the regime where the passive phase is isotropic. We show that activity leads to the emergence of nematic order and of spontaneous rotation in both two and three dimensions. In two dimensions the rotation is caused by the formation of a chiral +1 defect at the center of the drop. With increasing activity, the droplet deforms to an ellipse and then to a rotating annulus. Growing droplets form extended active arms which loop around to produce holes. In three dimensions the rotation is due to a disclination which loops away from and back to the surface, defining the rotation axis. In the bulk the disclination loop ends at a skyrmion. Active extensile flows deform the droplet to an oblate ellipsoid and contractile flows elongate it along the rotation axis. We compare our results on rotation in two-dimensional droplets with experiments on microtubule and motor protein suspensions and find a critical radius approximately equal to 700µm, above which the spontaneous rotation gives way to active turbulence. Comparing the simulation parameters with experiments on epithelial cell colonies shows that the crossover radius for cell colonies could be as large as 2mm, in agreement with experiments.