Effect of model parameters. The concentration of predicted free VEGF in the interstitium is sensitive to the presence and density of receptors on abluminal and luminal endothelial surfaces, and on myocytes and tumor cells. Baseline Model 1 is based on , and Baseline Model 2 is based on . In the baseline models, receptor density is assumed to be: 10,000 VEGFR1, 10,000 VEGFR2, and 100,000 NRP1 molecules/endothelial cell. Experimental receptor density is based on in vitro in human cells using quantitative flow cytometry  and in vivo quantification in mouse skeletal muscle and tumor xenografts using the same technique. In each simulation, VEGF secretion is tuned to maintain blood free VEGF at 4.5 pM. Simulation cases are as follows: A, VEGFR1, VEGFR2, and NRP1 present on abluminal endothelial surface with assumed receptor density. B, VEGFR1, VEGFR2, and NRP1 present on abluminal endothelial surface with experimental receptor density. C, VEGFR1, VEGFR2, and NRP1 evenly distributed on abluminal and luminal endothelial surface with assumed receptor density. D, VEGFR1, VEGFR2, and NRP1 evenly distributed on abluminal and luminal endothelial surface with experimental receptor density. Cases E through K build upon the previous case by sequentially refining the model: E, Addition of NRP1 on myocytes. F, Addition of VEGFR1 on tumor cells. G, Addition of VEGFR2 present on tumor cells. H, Addition of NRP1 on tumor cells. I, Addition of NRP2 on tumor cells. J, Incorporation of VEGF degradation in normal tissue and tumor. K, Incorporation of experimental data for VEGF secretion by tumor cells (Current Model).
Finley et al. BMC Systems Biology 2011 5:193 doi:10.1186/1752-0509-5-193