A Computational Model of FGF-2 Binding and HSPG Regulation Under Flow

A novel convection--diffusion--reaction model is developed to simulate fibroblast growth factor (FGF-2) binding to cell surface receptors (FGFRs) and heparan sulfate proteoglycans (HSPGs) under flow conditions within a cylindrical-shaped vessel or capillary. The model consists of a set of coupled nonlinear partial differential equations (PDEs) and a set of coupled nonlinear ordinary differential equations (ODEs). The time-dependent PDE system is discretized and solved by a second-order implicit Euler scheme using the finite volume method. The ODE system is solved by a stiff ODE solver VODE using backward differencing formulation (BDF). The transient solution of FGF-2, FGFR, HSPG, and their bound complexes for three different flow rates are computed and presented. Simulation results indicate that the model can predict growth factor transport and binding to receptors with/without the presence of heparan sulfate, as well as the effect of flow rate on growth factor-receptor binding. Our computational model may provide a useful means to investigate the impact of fluid flow on growth factor dynamics, and ultimately, signaling within the circulation.