A theoretical model of cytosolic calcium elevation following wounding in urothelial cell monolayers

Peter A. Appleby*, Saqib Shabir, Jennifer Southgate, Dawn Walker

*Corresponding author for this work

Research output: Contribution to journalConference articlepeer-review

Abstract

Scratch wounding of a urothelial cell monolayer triggers a number of events including the release of soluble, diffusible signalling factors and mechanical stimulation of cells at the wound edge. These events cause a sustained elevation in cytosolic calcium concentration in the cells surrounding the wound and a transient rise in those further away. The precise form of this calcium transient is believed to play a central role in determining the subsequent response of individual cells and ultimately leads to a co-ordinated, population-level response that rapidly closes the wound. Here we present a framework for modelling the initial phases of this process. We combine a PDE model of diffusion in the extracellular medium and an ODE model of calcium signalling that has been tailored to represent urothelial cells. The ODE model is capable of generating a wide range of calcium transients, including spikes, bursts, oscillations and sustained elevations in the cytosolic calcium concentration. In multi-cell simulations of scratch wounding in a perfusion flow we find that the spatial position of the cells relative to the wound site leads to distinct classes of calcium response, with cells proximal to the wound exhibiting a sustained elevation and cells distal to the wound exhibiting a more transient elevation. We compare these results to existing experimental data and generate a number of novel predictions that could be used to test the model experimentally.

Original languageEnglish
Article number012168
JournalJournal of Physics: Conference Series
Volume410
Issue number1
DOIs
Publication statusPublished - 2013
Event1st International Conference on Mathematical Modelling in Physical Sciences, IC-MSQUARE 2012 - Budapest, Hungary
Duration: 3 Sept 20127 Sept 2012

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