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.

Modelling the evolution of uncertainty levels during design

Design work involves uncertainty that arises from, and influences, the progressive development of solutions. This paper analyses the influences of evolving uncertainty levels on the design process. We focus on uncertainties associated with choosing the values of design parameters, and do not consider in detail the issues that arise when parameters must first be identified. Aspects of uncertainty and its evolution are discussed, and a new task-based model is introduced to describe process behaviour in terms of changing uncertainty levels. The model is applied to study two process configuration problems based on aircraft wing design: one using an analytical solution and one using Monte-Carlo simulation. The applications show that modelling uncertainty levels during design can help assess management policies, such as how many concepts should be considered during design and to what level of accuracy. © 2011 Springer-Verlag.