Quantifying the roles of cell motility and cell proliferation in a circular barrier assay

Author:

Simpson Matthew J.12,Treloar Katrina K.12,Binder Benjamin J.3,Haridas Parvathi2,Manton Kerry J.2,Leavesley David I.2,McElwain D. L. Sean2,Baker Ruth E.4

Affiliation:

1. School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia

2. Tissue Repair and Regeneration Program, Queensland University of Technology, Brisbane, Australia

3. School of Mathematical Sciences, University of Adelaide, Adelaide, Australia

4. Centre for Mathematical Biology, Mathematical Institute, University of Oxford, 24–29 St Giles’, Oxford OX1 3LB, UK

Abstract

Moving fronts of cells are essential features of embryonic development, wound repair and cancer metastasis. This paper describes a set of experiments to investigate the roles of random motility and proliferation in driving the spread of an initially confined cell population. The experiments include an analysis of cell spreading when proliferation was inhibited. Our data have been analysed using two mathematical models: a lattice-based discrete model and a related continuum partial differential equation model. We obtain independent estimates of the random motility parameter, D , and the intrinsic proliferation rate, λ , and we confirm that these estimates lead to accurate modelling predictions of the position of the leading edge of the moving front as well as the evolution of the cell density profiles. Previous work suggests that systems with a high λ / D ratio will be characterized by steep fronts, whereas systems with a low λ / D ratio will lead to shallow diffuse fronts and this is confirmed in the present study. Our results provide evidence that continuum models, based on the Fisher–Kolmogorov equation, are a reliable platform upon which we can interpret and predict such experimental observations.

Publisher

The Royal Society

Subject

Biomedical Engineering,Biochemistry,Biomaterials,Bioengineering,Biophysics,Biotechnology

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