Collective Cell Migration: Leadership, Invasion and Segregation

A number of biological processes, such as embryo development, cancer metastasis or wound healing, rely on cells moving in concert. The mechanisms leading to the emergence of coordinated motion remain however largely unexplored. Although biomolecular signalling is known to be involved in most occurrences of collective migration, the role of physical and mechanical interactions has only been recently investigated. In this paper, a versatile framework for cell motility is implemented in-silico in order to study the minimal requirements for the coordination of a group of epithelial cells. We find that cell motility and cell-cell mechanical interactions are sufficient to generate a broad array of behaviours commonly observed in vitro and in vivo. Cell streaming, sheet migration and susceptibility to leader cells are examples of behaviours spontaneously emerging from these simple assumptions, which might explain why collective effects are so ubiquitous in nature. This analysis provides also new insights into cancer metastasis and cell sorting, suggesting in particular that collective invasion might result from an emerging coordination in a system where single cells are mechanically unable to invade.

Emerging modes of collective cell migration induced by geometrical constraints.

The role of geometrical confinement on collective cell migration has been recognized but has not been elucidated yet. Here, we show that the geometrical properties of the environment regulate the formation of collective cell migration patterns through cell-cell interactions. Using microfabrication techniques to allow epithelial cell sheets to migrate into strips whose width was varied from one up to several cell diameters, we identified the modes of collective migration in response to geometrical constraints. We observed that a decrease in the width of the strips is accompanied by an overall increase in the speed of the migrating cell sheet. Moreover, large-scale vortices over tens of cell lengths appeared in the wide strips whereas a contraction-elongation type of motion is observed in the narrow strips. Velocity fields and traction force signatures within the cellular population revealed migration modes with alternative pulling and/or pushing mechanisms that depend on extrinsic constraints. Force transmission through intercellular contacts plays a key role in this process because the disruption of cell-cell junctions abolishes directed collective migration and passive cell-cell adhesions tend to move the cells uniformly together independent of the geometry. Altogether, these findings not only demonstrate the existence of patterns of collective cell migration depending on external constraints but also provide a mechanical explanation for how large-scale interactions through cell-cell junctions can feed back to regulate the organization of migrating tissues.

Local stability results for the collective behaviors of infinite populations of pulse-coupled oscillators

In this paper, we investigate the behavior of pulse-coupled integrate-and-fire oscillators. Because the stability analysis of finite populations is intricate, we investigate stability results in the approximation of infinite populations. In addition to recovering known stability results of finite populations, we also obtain new stability results for infinite populations. In particular, under a weak coupling assumption, we solve for the continuum model a conjecture still prevailing in the finite dimensional case. © 2011 IEEE.

Stabilization of planar collective motion with limited communication

This paper proposes a design methodology to stabilize relative equilibria in a model of identical, steered particles moving in the plane at unit speed. Relative equilibria either correspond to parallel motion of all particles with fixed relative spacing or to circular motion of all particles around the same circle. Particles exchange relative information according to a communication graph that can be undirected or directed and time-invariant or time-varying. The emphasis of this paper is to show how previous results assuming all-to-all communication can be extended to a general communication framework. © 2008 IEEE.

Stabilization of collective motion in three dimensions: A consensus approach

This paper proposes a methodology to stabilize relative equilibria in a model of identical, steered particles moving in three-dimensional Euclidean space. Exploiting the Lie group structure of the resulting dynamical system, the stabilization problem is reduced to a consensus problem. We first derive the stabilizing control laws in the presence of all-to-all communication. Providing each agent with a consensus estimator, we then extend the results to a general setting that allows for unidirectional and time-varying communication topologies. © 2007 IEEE.

Oscillator models and collective motion

A description of the so called "particles with coupled oscillator dynamics" (PCOD) is presented which is used to model, analyze and synthesize collective motion. An oscillator model with spatial dynamics is presented to help describe how to design steering control laws while it is being used to study biological collectives. Lastly, both engineering and biological analysis were described.

Stabilization of planar collective motion: All-to-all communication

This paper proposes a design methodology to stabilize isolated relative equilibria in a model of all-to-all coupled identical particles moving in the plane at unit speed. Isolated relative equilibria correspond to either parallel motion of all particles with fixed relative spacing or to circular motion of all particles with fixed relative phases. The stabilizing feedbacks derive from Lyapunov functions that prove exponential stability and suggest almost global convergence properties. The results of the paper provide a low-order parametric family of stabilizable collectives that offer a set of primitives for the design of higher-level tasks at the group level. © 2007 IEEE.

Collective motion, sensor networks, and ocean sampling

This paper addresses the design of mobile sensor networks for optimal data collection. The development is strongly motivated by the application to adaptive ocean sampling for an autonomous ocean observing and prediction system. A performance metric, used to derive optimal paths for the network of mobile sensors, defines the optimal data set as one which minimizes error in a model estimate of the sampled field. Feedback control laws are presented that stably coordinate sensors on structured tracks that have been optimized over a minimal set of parameters. Optimal, closed-loop solutions are computed in a number of low-dimensional cases to illustrate the methodology. Robustness of the performance to the influence of a steady flow field on relatively slow-moving mobile sensors is also explored © 2006 IEEE.

Collective optimization over average quantities

This paper addresses the design of algorithms for the collective optimization of a cost function defined over average quantities in the presence of limited communication. We argue that several meaningful collective optimization problems can be formulated in this way. As an application of the proposed approach, we propose a novel algorithm that achieves synchronization or balancing in phase models of coupled oscillators under mild connectedness assumptions on the (possibly time-varying and unidirectional) communication graphs. © 2006 IEEE.

Collective motion of self-propelled particles: Stabilizing symmetric formations on closed curves

We provide feedback control laws to stabilize formations of multiple, unit speed particles on smooth, convex, and closed curves with definite curvature. As in previous work we exploit an analogy with coupled phase oscillators to provide controls which isolate symmetric particle formations that are invariant to rigid translation of all the particles. In this work, we do not require all particles to be able to communicate; rather we assume that inter-particle communication is limited and can be modeled by a fixed, connected, and undirected graph. Because of their unique spectral properties, the Laplacian matrices of circulant graphs play a key role. The methodology is demonstrated using a superellipse, which is a type of curve that includes circles, ellipses, and rounded rectangles. These results can be used in applications involving multiple autonomous vehicles that travel at constant speed around fixed beacons. ©2006 IEEE.

Oscillator models and collective motion: Splay state stabilization of self-propelled particles

This paper presents a Lyapunov design for the stabilization of collective motion in a planar kinematic model of N particles moving at constant speed. We derive a control law that achieves asymptotic stability of the splay state formation, characterized by uniform rotation of N evenly spaced particles on a circle. In designing the control law, the particle headings are treated as a system of coupled phase oscillators. The coupling function which exponentially stabilizes the splay state of particle phases is combined with a decentralized beacon control law that stabilizes circular motion of the particles. © 2005 IEEE.

Collective motion: Bistability and trajectory tracking

This paper presents analysis and application of steering control laws for a network of self-propelled, planar particles. We explore together the two stably controlled group motions, parallel motion and circular motion, for modeling and design purposes. We show that a previously considered control law simultaneously stabilizes both parallel and circular group motion, leading to Instability and hysteresis. We also present behavior primitives that enable piecewise-linear network trajectory tracking.