Multiple types of data are required to identify the mechanisms influencing the spatial expansion of melanoma cell colonies

BMC Systems Biology

Ruth E Baker¹  DL Sean McElwain²  David I Leavesley²  Kerry J Manton²  Parvathi Haridas²  Matthew J Simpson²  Katrina K Treloar² 

[1] Centre for Mathematical Biology, Mathematical Institute, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK;Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia

关键词: Mathematical model;    Circular barrier assay;    Cell–to–cell adhesion;    Cell proliferation;    Cell migration;    Cancer;    Melanoma;   

Others  :  1141706
DOI  :  10.1186/1752-0509-7-137

 received in 2013-09-11, accepted in 2013-12-05,  发布年份 2013

【 摘 要 】

Background

The expansion of cell colonies is driven by a delicate balance of several mechanisms including cell motility, cell–to–cell adhesion and cell proliferation. New approaches that can be used to independently identify and quantify the role of each mechanism will help us understand how each mechanism contributes to the expansion process. Standard mathematical modelling approaches to describe such cell colony expansion typically neglect cell–to–cell adhesion, despite the fact that cell–to-cell adhesion is thought to play an important role.

Results

We use a combined experimental and mathematical modelling approach to determine the cell diffusivity, D, cell–to–cell adhesion strength, q, and cell proliferation rate, λ, in an expanding colony of MM127 melanoma cells. Using a circular barrier assay, we extract several types of experimental data and use a mathematical model to independently estimate D, q and λ. In our first set of experiments, we suppress cell proliferation and analyse three different types of data to estimate D and q. We find that standard types of data, such as the area enclosed by the leading edge of the expanding colony and more detailed cell density profiles throughout the expanding colony, does not provide sufficient information to uniquely identify D and q. We find that additional data relating to the degree of cell–to–cell clustering is required to provide independent estimates of q, and in turn D. In our second set of experiments, where proliferation is not suppressed, we use data describing temporal changes in cell density to determine the cell proliferation rate. In summary, we find that our experiments are best described using the range D=161−243μm²hour⁻¹, q=0.3−0.5 (low to moderate strength) and λ=0.0305−0.0398hour⁻¹, and with these parameters we can accurately predict the temporal variations in the spatial extent and cell density profile throughout the expanding melanoma cell colony.

Conclusions

Our systematic approach to identify the cell diffusivity, cell–to–cell adhesion strength and cell proliferation rate highlights the importance of integrating multiple types of data to accurately quantify the factors influencing the spatial expansion of melanoma cell colonies.

【 授权许可】

   
2013 Treloar et al.; licensee BioMed Central Ltd.

【 图 表 】

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