Collective cell migration occurs in a diversity of physiological processes such as wound healing, cancer metastasis, and embryonic morphogenesis. In the collective context, cohesive cells may move as a translational solid, swirl as a fluid, or even rotate like a disk, with scales ranging from several to dozens of cells. In this work, an active vertex model is presented to explore the regulatory roles of social interactions of neighboring cells and environmental confinements in collective cell migration in a confluent monolayer. It is found that the competition between two kinds of intercellular social interactions-local alignment and contact inhibition of locomotion-drives the cells to self-organize into various dynamic coherent structures with a spatial correlation scale. The interplay between this intrinsic length scale and the external confinement dictates the migration modes of collective cells confined in a finite space. We also show that the local alignment-contact inhibition of locomotion coordination can induce giant density fluctuations in a confluent cell monolayer without gaps, which triggers the spontaneous breaking of orientational symmetry and leads to phase separation.

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Investigation of energy mechanisms at the collective cell scale is a challenge for understanding various biological processes, such as embryonic development and tumor metastasis. Here we investigate the energetics of self-sustained mesoscale turbulence in confluent two-dimensional (2D) cell monolayers. We find that the kinetic energy and enstrophy of collective cell flows in both epithelial and non-epithelial cell monolayers collapse to a family of probability density functions, which follow the q-Gaussian distribution rather than the Maxwell–Boltzmann distribution. The enstrophy scales linearly with the kinetic energy as the monolayer matures. The energy spectra exhibit a power-decaying law at large wavenumbers, with a scaling exponent markedly different from that in the classical 2D Kolmogorov–Kraichnan turbulence. These energetic features are demonstrated to be common for all cell types on various substrates with a wide range of stiffness. This study provides unique clues to understand active natures of cell population and tissues.

Oscillatory morphodynamics provides necessary mechanical cues for many multicellular processes. Owing to their collective nature, these processes require robustly coordinated dynamics of individual cells, which are often separated too distantly to communicate with each other through biomaterial transportation. Although it is known that the mechanical balance generally plays a significant role in the systems' morphologies, it remains elusive whether and how the mechanical components may contribute to the systems' collective morphodynamics. Here, we study the collective oscillations in the Drosophila amnioserosa tissue to elucidate the regulatory roles of the mechanical components. We identify that the tensile stress is the key activator that switches the collective oscillations on and off. This regulatory role is shown analytically using the Hopf bifurcation theory. We find that the physical properties of the tissue boundary are directly responsible for synchronizing the oscillatory intensity and polarity of all inner cells and for orchestrating the spatial oscillation patterns in the tissue.collective cell oscillations | morphodynamics | Hopf bifurcation M orphodynamics describes how a subject's form changes over time. In living systems, the morphodynamic changes are both the effect and the cause of coordinated biochemical and biophysical processes. On the one hand, a system's morphological changes result from intracellular force generation and intercellular force transmission through sequences of biological events. On the other hand, the morphodynamic changes provide various mechanical and physical cues that are critical for the morphogenesis of multicellular tissues (1, 2) and the development of organisms (3-5). Owing to the collective nature of many biological processes, it is of profound interest to understand the principle underlying the morphodynamics of a living thing that is built from individual yet coherent cells (6-8).Oscillatory morphodynamics is an important category of collective morphodynamic phenomena that exists in many biological systems, including vertebrate segmentation (9), mesoderm invagination (10), and germband extension (11). These morphological oscillations are rooted in the active contraction of the actomyosin cytoskeleton in individual cells (12)(13)(14)(15) and are often coupled with other intracellular biochemical signaling pathways (9,13,14). During the oscillatory process, the actomyosin cytoskeleton gets activated and forms an apical network beneath the membrane, which further facilitates the formation of cell-cell junctions that allow force transmission from a cell to its neighbors (16). These observations have motivated many modeling efforts that generally fall into two categories: The couplingbased models attempt to couple membrane tension with the actomyosin regulation pathway to reproduce the oscillation of single or multiple cells (14, 17); the input-based ratchet models treat the cortical actin-myosin cytoskeleton or the supracellular actin cable as a programed machine tha...

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