Title :
A Computational Model of FGF-2 Binding and HSPG Regulation Under Flow
Author :
Shen, Wensheng ; Zhang, Changjiang ; Fannon, Michael W. ; Forsten-Williams, Kimberly ; Jun Zhang
Author_Institution :
Coll. at Brockport, Dept. of Comput. Sci., State Univ. of New York, Brockport, NY, USA
Abstract :
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.
Keywords :
blood vessels; cellular biophysics; finite volume methods; haemodynamics; haemorheology; partial differential equations; FGF-2 binding; HSPG regulation; backward differencing formulation; capillary; cell surface receptors; coupled nonlinear partial differential equations; cylindrical-shaped vessel; fibroblast growth factor; finite volume method; fluid flow; growth factor dynamics; heparan sulfate proteoglycans; second-order implicit Euler scheme; time-dependent PDE; transient solution; Biomembranes; Computational modeling; Computer science; Couplings; Differential equations; Diseases; Ear; Fibroblasts; Mathematical model; Neoplasms; Partial differential equations; Postal services; Predictive models; World Wide Web; Computer modeling; convection diffusion reaction; fibroblast growth factor (FGF-2); heparan sulfate proteoglycan (HSPG); incompressible flow; Algorithms; Bioreactors; Computer Simulation; Fibroblast Growth Factor 2; Heparan Sulfate Proteoglycans; Kinetics; Ligands; Models, Biological; Nonlinear Dynamics; Protein Binding; Receptors, Fibroblast Growth Factor; Reproducibility of Results; Rheology;
Journal_Title :
Biomedical Engineering, IEEE Transactions on
DOI :
10.1109/TBME.2008.2002109