Figure 1. Parameter optimization and summary of reaction network.

A) Optimization of modeling parameters based upon sensitivity analysis and ODE solution. Green line: Kinetics of Shc phosphorylation in EGF-stimulated hepatocytes (20 nM EGF) as determined by Kholodenko et al. [12]. Red line: results obtained using the ODE model of [12]. Blue line: improved fit of ODE solution to experimental data after incorporation of receptor degradation reactions. B) Summary of reaction network in the ODE and CSNSA models. Note that, in the spatial CSNSA model, stars mark membrane reactions handled by the spatial stochastic Monte Carlo algorithm. All remaining reactions are governed by the Gillespie algorithm. Additional reactions that were added to the original ODE model from Kholodenko et al. [12] are shown in blue. Numbering of reactions is arbitrary.