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.

A probabilistic energy model for non-domestic building sectors applied to analysis of school buildings in greater London

The diversity of non-domestic buildings at urban scale poses a number of difficulties to develop models for large scale analysis of the stock. This research proposes a probabilistic, engineering-based, bottom-up model to address these issues. In a recent study we classified London's non-domestic buildings based on the service they provide, such as offices, retail premise, and schools, and proposed the creation of one probabilistic representational model per building type. This paper investigates techniques for the development of such models. The representational model is a statistical surrogate of a dynamic energy simulation (ES) model. We first identify the main parameters affecting energy consumption in a particular building sector/type by using sampling-based global sensitivity analysis methods, and then generate statistical surrogate models of the dynamic ES model within the dominant model parameters. Given a sample of actual energy consumption for that sector, we use the surrogate model to infer the distribution of model parameters by inverse analysis. The inferred distributions of input parameters are able to quantify the relative benefits of alternative energy saving measures on an entire building sector with requisite quantification of uncertainties. Secondary school buildings are used for illustrating the application of this probabilistic method. © 2012 Elsevier B.V. All rights reserved.