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.

The prediction of hot streak migration in a high-pressure turbine

Accurate predictions of combustor hot streak migration enable the turbine designer to identify high-temperature regions that can limit component life. It is therefore important that these predictions are achieved within the short time scales of a design process. This article compares temperature measurements of a circular hot streak through a turning duct and a research turbine with predictions using a three-dimensional Reynolds-averaged Navier-Stokes solver. It was found that the mixing length turbulence model did not predict the hot streak dissipation accurately. However, implementation of a very simple model of the free stream turbulence (FST) significantly improved the exit temperature predictions on both the duct and research turbine. One advantage of the simple FST model described over more complex alternatives is that no additional equations are solved. This makes the method attractive for design purposes, as it is not associated with any increase in computational time.

Hot streak and vane coolant migration in a downstream rotor

This paper describes a method of improving the cooling of the hub region of high-pressure turbine (HPT) rotor by making better use of the unsteady coolant flows originating from the upstream vane. The study was performed computationally on an engine HPT stage with representative inlet hot streak and vane coolant conditions. An experimental validation study of hot streak migration was undertaken on two low-speed test facilities. The unsteady mechanisms that transport hot and cold fluid within the rotor hub region are first examined. It was found that vortex-blade interaction dominated the unsteady transport of hot and cold fluid in the rotor hub region. This resulted in the transport of hot fluid onto the rotor hub and pressure surface, causing a peak in the surface gas temperatures. The vane film coolant was found to have only a limited effect in cooling this region. A new cooling configuration was thus examined which exploits the unsteadiness in rotor hub to aid transport of coolant towards regions of high rotor surface temperatures. The new coolant was introduced from a slot upstream of the vane. This resulted in the feed of slot coolant at a different phase and location relative to the vane film coolant within the rotor. The slot coolant was entrained into the unsteady rotor secondary flows and transported towards the rotor hub-pressure surface region. The slot coolant reduced the peak time-averaged rotor temperatures by a similar amount as the vane film coolant despite having only a sixth of the coolant mass flow. Copyright © 2008 by ASME.

Seismic model parameter estimation using least-squares migration

We describe a method for verifying seismic modelling parameters. It is equivalent to performing several iterations of unconstrained least-squares migration (LSM). The approach allows the comparison of modelling/imaging parameter configurations with greater confidence than simply viewing the migrated images. The method is best suited to determining discrete parameters but can be used for continuous parameters albeit with greater computational expense.

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.