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.
Shen
Wensheng
W
Department of Computational Science, State University of New York College at Brockport, Brockport, NY 14420, USA. wshen@brockport.edu
Zhang
Changjiang
C
Fannon
Michael W
MW
Forsten-Williams
Kimberly
K
Zhang
Jun
J
D000465:Algorithms; D019149:Bioreactors; D003198:Computer Simulation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D017711:Nonlinear Dynamics; D011485:Protein Binding; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015203:Reproducibility of Results; D012212:Rheology
D019812:Heparan Sulfate Proteoglycans; D008024:Ligands; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2