Epidermal growth factor binding and trafficking dynamics in fibroblasts: relationship to cell proliferation

Abstract

We provide a mathematical model, with accompanying quantitative experimental data, for binding and trafficking properties of the epidermal growth factor (EGF) receptor on B82 fibroblasts, and propose a theoretical dependence of cell proliferation rate on these properties. The signal for cell proliferation is generated by intrinsic EGF-receptor (EGFR) tyrosine kinase activation via EGF binding at the cell surface, and terminated by receptor/growth factor complex internalization and degradation. Our model consists of kinetic equations which describe the binding, internalization, and recycling of EGF and EGFR, along with a simple expression relation the dependence of cell cycle progression on EGFR dynamics. We show that, with key model parameters determined independently from EGF/fibroblast binding and internalization experiments, our model successfully predicts, as a first step, kinetic data for EGF binding to and internalization by B82 cells at 37°C.