Activation and synchronization of the oscillatory morphodynamics in multicellular monolayer

Abstract

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...

Dynamic Migration Modes of Collective Cells

“…In our study, we do not involve the detailed biochemical signaling pathways. Recent work on Drosophila amnioserosa and MDCK monolayers identified the critical role of intracellular contraction and polarity in epithelial morphogenesis (31,57). In fact, cell contractility as well as cell polarity is related to the complicated intracellular signaling pathways and transmembrane transport of signaling molecules (58,59).…”

“…where K a denotes the area stiffness of a cell, A 0 refers to the reference area, and A J is the current area of the J-th cell; K c represents the contractile modulus of a cell, and L J is the perimeter of the J-th cell; L quantifies the interfacial tension between neighboring cells, and l ij is the edge length of the cell-cell interface ij connecting vertices i and j. It is noted that the cell contractile modulus, K c , could also be time-dependent and regulated by biochemical cues such as the r-ROCK signaling pathway (31,33). For the sake of simplicity, however, we take a constant value of K c in the following analysis.…”

Intercellular Connectivity and Multicellular Bioelectric Oscillations in Nonexcitable Cells: A Biophysical Model

“…In this context, we must note that biomechanical oscillations in cell monolayers can also show a collective dynamics regulation. 62 In our case, the external regulation and collective control of depolarized/polarized cell states should be of biological significance because of the instructive role of membrane potentials in cell proliferation and differentiation, 6 − 8 the plasticity of predifferentiated mesenchymal stem cells, 9 and regeneration processes. 4 …”

Epithelial Tissues as Active Solids: From Nonlinear Contraction Pulses to Rupture Resistance

“…These evidence include contraction fronts in drosophila embryo during development [2] and density waves in MDCK cell monolayers in-vitro, either in confinement [3,4], during expansion [4,5] or under substrate-shear [6]. Theoretical works suggest models to explain the contractile patterns [7][8][9][10][11], models that include mechanical alongside chemical fields, diffusion or active transport. Note, that all these systems, and the suggested models, exhibit dynamics in time scales of minutes to hours.…”