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Experimental and multiscale modelling investigation exploring the role of pioneer cells in a moving cell front

Most mathematical models of collective cell spreading make the standard assumption that the cell diffusivity and cell proliferation rate are constants that do not vary across the cell population. Here we present a combined experimental and mathematical modeling study which aims to investigate how differences in the cell diffusivity and cell proliferation rate amongst a population of cells can impact the collective behavior of the population. We present data from a three–dimensional transwell migration assay which suggests that the cell diffusivity of some groups of cells within the population are larger than the cell diffusivity of other groups of cells within the population. Using this information, we explore the consequences of explicitly representing this variability in a mathematical model of a scratch assay where we treat the total population of cells as two possibly distinct subpopulations. Our results show that when we make the standard assumption that all cells within the population behave identically we observe the formation of moving fronts of cells where both subpopulations are well–mixed and indistinguishable. In contrast, when we consider the same system where the two subpopulations are distinct, we observe a very different outcome where the spreading population becomes spatially organized with the more motile subpopulation dominating at the leading edge while the less motile subpopulation is practically absent from the leading edge. To provide a different perspective on our discrete simulation results, we derive an approximate partial differential equation description of the averaged behaviour of our discrete model and show that we observe a good match between the averaged discrete simulation data and the solution of the partial differential equation model.

 

This is joint work with Ms Parvathi Haridas and Professor Sean McElwain, and a complete description of the results can be found in Simpson, Haridas and McElwain (2014) Do pioneer cells exist? PLoS ONE. 9(1): e85488. 

Matthew Simpson

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