Cell-Centred Modeling of Tissue Behaviour

Abstract

Normal structure and function in epithelial tissues is an emergent property of the interaction of the cells which comprise the tissue, so a cell-centred approach to the modelling of tissue behaviour is a logical approach. Epithelial tissues have the advantage, as a starting point, that they are relatively simple, but also have significant clinical problems - wound healing and the development of malignancy in particular - but also many other problems because of their barrier function. Exemplar biological systems are skin and urothelium. An individual-based modelling approach is adopted, with a 1:1 correspondence between living cells in biological (in vitro) models and the software agents used to represent the cells. The software agents are a formal entity (a communicating stream X-machine); the models are described using a mark-up language; and a formal framework and associated tools have been developed for model execution. ODE and PDE models of any complexity (e.g., biochemical models of signalling pathways) can be called as functions within the individual agents, and the physical environment of the cells can be modelled either globally or as a physical model of interaction with neighbouring cells that is embedded within each agent. The realisation is inherently parallel, and is also being used to model cell signalling, the behaviour of social insects, and macro-economic behaviour.