Figure 7
Competing influences of HSPG binding and VEGF cleavage on biological responses. Experimental evidence indicates that HSPG binding and VEGF cleavage modulate the same axis of vascular phenotypes (A) [6, 7, 13, 17]. To understand how the VEGF distribution may be responsible for vessel patterning, we measured various metrics of the VEGF distribution as they would vary either with variation in the HSPG affinity of the secreted isoform (with MMP activity held constant at kP = 2.8·10-4 s-1, dash-dotted lines) or with variation in the background proteolytic activity (kP ranged from 10-6 s-1 and 10-2 s-1, assuming that VEGF165 is secreted). The HSPG-binding-only model (B) and the matrix-sequestered VEGF degradation model (C) were considered. Circle markers indicate respective positions of (from left to right) VEGF189, VEGF165, and VEGF121 (Kd = ∞). Control cases simulated in the absence of MMPs are given in solid lines. Yellow boxes in B and C indicate the range where bound VEGF does not display behavior consistent with the experimental data. Simulations were performed in the absence of receptors, the presence of which would have a negligible impact on the VEGF distribution, to obtain computational efficiency permitting simulation of a broad range of parameters (parameters given in Table 4).