Journal
JOURNAL OF THEORETICAL BIOLOGY
Volume 538, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2021.110996
Keywords
Mathematical pharmacology; Receptor theory; Differential equations; Perturbation methods; Dimerisation
Categories
Funding
- College of Science PhD studentship at Swansea University
- Faculty of Environment and Technology funding award at UWE Bristol
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In this paper, a mathematical model representing the binding of VEGF to VEGFR and the subsequent ligand-induced dimerisation is presented. The qualitative and quantitative effect of binding cooperativity is a key factor in this work. The ordinary differential equation system is analyzed at equilibrium, and numerical methods are used to study time-course dynamics. Perturbation analysis is employed to understand the complexities of the behaviors. The simulation results validate the model by showing an excellent fit to experimental data.
The vascular endothelial growth factor (VEGF) receptor (VEGFR) system plays a role in cancer and many other diseases. It is widely accepted that VEGFR receptors dimerise in response to VEGF binding. However, analysis of these mechanisms and their implications for drug development still requires further exploration. In this paper, we present a mathematical model representing the binding of VEGF to VEGFR and the subsequent ligand-induced dimerisation. A key factor in this work is the qualitative and quantitative effect of binding cooperativity, which describes the effect that the binding of a ligand to a receptor has on the binding of that ligand to a second receptor, and the dimerisation of these receptors. We analyse the ordinary differential equation system at equilibrium, giving analytical solutions for the total amount of ligand bound. For time-course dynamics, we use numerical methods to explore possible behaviours under various parameter regimes, while perturbation analysis is used to understand the intricacies of these behaviours. Our simulation results show an excellent fit to experimental data, towards validating the model. (C) 2021 The Author(s). Published by Elsevier Ltd.
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