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Individual-based and continuum models of phenotypically heterogeneous growing cell populations

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Date
18/03/2022
Author
Macfarlane, Fiona Ruth
Funder
The Royal Society of Edinburgh
Grant ID
1879
Keywords
Growing cell populations
Travelling waves
Non-local partial differential equations
Continuum models
Phenotypic heterogeneity
Individual-based models
QA Mathematics
QH301 Biology
T-NDAS
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Abstract
Existing comparative studies between individual-based models of growing cell populations and their continuum counterparts have mainly been focused on homogeneous populations, in which all cells have the same phenotypic characteristics. However, significant intercellular phenotypic variability is commonly observed in cellular systems. In light of these considerations, we develop here an individual-based model for the growth of phenotypically heterogeneous cell populations. In this model, the phenotypic state of each cell is described by a structuring variable that captures intercellular variability in cell proliferation and migration rates. The model tracks the spatial evolutionary dynamics of single cells, which undergo pressure-dependent proliferation, heritable phenotypic changes and directional movement in response to pressure differentials. We formally show that the continuum limit of this model comprises a non-local partial differential equation for the cell population density function, which generalises earlier models of growing cell populations. We report on the results of numerical simulations of the individual-based model which illustrate how proliferation-migration tradeoffs shaping the evolutionary dynamics of single cells can lead to the formation, at the population level, of travelling waves whereby highly-mobile cells locally dominate at the invasive front, while more-proliferative cells are found at the rear. Moreover, we demonstrate that there is an excellent quantitative agreement between these results and the results of numerical simulations and formal travelling-wave analysis of the continuum model, when sufficiently large cell numbers are considered. We also provide numerical evidence of scenarios in which the predictions of the two models may differ due to demographic stochasticity, which cannot be captured by the continuum model. This indicates the importance of integrating individual-based and continuum approaches when modelling the growth of phenotypically heterogeneous cell populations.
Citation
Macfarlane , F R 2022 , ' Individual-based and continuum models of phenotypically heterogeneous growing cell populations ' , AIMS Bioengineering , vol. 9 , no. 1 , pp. 68-92 . https://doi.org/10.3934/bioeng.2022007
Publication
AIMS Bioengineering
Status
Peer reviewed
DOI
https://doi.org/10.3934/bioeng.2022007
ISSN
2375-1495
Type
Journal article
Rights
Copyright © 2022 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0).
Description
T.L. gratefully acknowledges support from the MIUR grant “Dipartimenti di Eccellenza 2018-2022” (Project no. E11G18000350001). F.R.M. gratefully acknowledges support from the RSE Saltire Early Career Fellowship ‘Multiscale mathematical modelling of spatial eco-evolutionary cancer dynamics’ (Fellowship No. 1879).
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/25133

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