Spatial fluctuations at vertices of epithelial layers: quantification of regulation by Rho pathway

In living matter, shape fluctuations induced by acto-myosin are usually studied in vitro via reconstituted gels, whose properties are controlled by changing the concentrations of actin, myosin and cross-linkers. Such an approach deliberately avoids to consider the complexity of biochemical signaling inherent to living systems. Acto-myosin activity inside living cells is mainly regulated by the Rho signaling pathway which is composed of multiple layers of coupled activators and inhibitors. We investigate how such a pathway controls the dynamics of confluent epithelial tissues by tracking the displacements of the junction points between cells. Using a phenomenological model to analyze the vertex fluctuations, we rationalize the effects of different Rho signaling targets on the emergent tissue activity by quantifying the effective diffusion coefficient, the persistence time and persistence length of the fluctuations. Our results reveal an unanticipated correlation between layers of activation/inhibition and spatial fluctuations within tissues. Overall, this work connects the regulation via biochemical signaling with mesoscopic spatial fluctuations, with potential application to the study of structural rearrangements in epithelial tissues.Comment: 8 pages, 3 figure

The long-time dynamics of two hydrodynamically-coupled swimming cells

Swimming micro-organisms such as bacteria or spermatozoa are typically found in dense suspensions, and exhibit collective modes of locomotion qualitatively different from that displayed by isolated cells. In the dilute limit where fluid-mediated interactions can be treated rigorously, the long-time hydrodynamics of a collection of cells result from interactions with many other cells, and as such typically eludes an analytical approach. Here we consider the only case where such problem can be treated rigorously analytically, namely when the cells have spatially confined trajectories, such as the spermatozoa of some marine invertebrates. We consider two spherical cells swimming, when isolated, with arbitrary circular trajectories, and derive the long-time kinematics of their relative locomotion. We show that in the dilute limit where the cells are much further away than their size, and the size of their circular motion, a separation of time scale occurs between a fast (intrinsic) swimming time, and a slow time where hydrodynamic interactions lead to change in the relative position and orientation of the swimmers. We perform a multiple-scale analysis and derive the effective dynamical system - of dimension two - describing the long-time behavior of the pair of cells. We show that the system displays one type of equilibrium, and two types of rotational equilibrium, all of which are found to be unstable. A detailed mathematical analysis of the dynamical systems further allows us to show that only two cell-cell behaviors are possible in the limit of $t\to\infty$, either the cells are attracted to each other (possibly monotonically), or they are repelled (possibly monotonically as well), which we confirm with numerical computations

Spatial Fluctuations at Vertices of Epithelial Layers: Quantification of Regulation by Rho Pathway

In living matter, shape fluctuations induced by acto-myosin are usually studied in vitro via reconstituted gels, whose properties are controlled by changing the concentrations of actin, myosin, and cross-linkers. Such an approach deliberately avoids consideration of the complexity of biochemical signaling inherent to living systems. Acto-myosin activity inside living cells is mainly regulated by the Rho signaling pathway which is composed of multiple layers of coupled activators and inhibitors. Here, we investigate how such a pathway controls the dynamics of confluent epithelial tissues by tracking the displacements of the junction points between cells. Using a phenomenological model to analyze the vertex fluctuations, we rationalize the effects of different Rho signaling targets on the emergent tissue activity by quantifying the effective diffusion coefficient, and the persistence time and length of the fluctuations. Our results reveal an unanticipated correlation between layers of activation/inhibition and spatial fluctuations within tissues. Overall, this work connects regulation via biochemical signaling with mesoscopic spatial fluctuations, with potential application to the study of structural rearrangements in epithelial tissues