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.

The role of infrastructure in improving human settlements

This paper considers how the provision of integrated household-level infrastructure – particularly water and environmental sanitation (including water supply, sewerage, roads, storm drainage and solid waste management) –can play a leading role in improving the conditions in slum settlements. Around 700 socio-economic interviews were carried out in India and South Africa to investigate an innovative approach called slum networking, which sees the strong correlation between slum locations and drainage paths as an opportunity for improving the wider urban environment. This recognition allows resources to be mobilised locally, thereby removing the need for external aid funding. The evidence from the 700 families shows that communities perceive water and sanitation inputs to be their top priority and are willing to contribute to the costs. If slum upgrading is led with access to integrated water and environmental sanitation at household level with community contributions to the cost of infrastructure, then slum communities subsequently invest considerably greater sums in improved housing and education, with longer term contributions to poverty alleviation, improvements in health and literacy and an increase in disposable incomes.

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.