TY - JOUR
T1 - A theoretical model of cytosolic calcium elevation following wounding in urothelial cell monolayers
AU - Appleby, Peter A.
AU - Shabir, Saqib
AU - Southgate, Jennifer
AU - Walker, Dawn
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875744897&partnerID=8YFLogxK
U2 - 10.1088/1742-6596/410/1/012168
DO - 10.1088/1742-6596/410/1/012168
M3 - Conference article
AN - SCOPUS:84875744897
SN - 1742-6588
VL - 410
JO - Journal of Physics: Conference Series
JF - Journal of Physics: Conference Series
IS - 1
M1 - 012168
T2 - 1st International Conference on Mathematical Modelling in Physical Sciences, IC-MSQUARE 2012
Y2 - 3 September 2012 through 7 September 2012
ER -