Figure 8

VEGFR2 and VEGFR1 signaling in mediating vascular phenotypes. Using the VEGF distributions calculated by the isoform-specific degradation model in Figure 7 we calculated VEGF binding to VEGFR2 (A) and VEGFR1 (B). We assume 10⁴ VEGFR2, 10⁴ VEGFR1, and 3*10⁴ NRP1 per tip cell (assuming no VEGF depletion by the sprout). VEGF isoforms show isoform-specific differences in their ability to bind NRP1 and the VEGFR1-NRP1 complex. To calculate the receptor binding parameters for arbitrary isoforms, we imposed two constraints to interpolate/extrapolate around the known VEGF isoforms (refer to Methods, Kinetic Parameters). VEGF/NRP1 affinity was made to recapitulate the lack of binding of VEGF₁₂₁ and stronger binding affinity of VEGF₁₈₉ [37]. VEGF binding affinity to the VEGFR1-NRP1 complex and NRP1 coupling to the VEGF-VEGFR1 complex was set such that VEGF₁₂₁ can fully bind to VEGFR1-NRP1 [95], while any isoform with greater HSPG affinity than that of VEGF₁₆₅ cannot bind. Circle markers indicate (from left to right) VEGF₁₈₉, VEGF₁₆₅, and VEGF₁₂₁ (K_d = ∞).