Figure 2

Schematic diagram of computational model. We simulate the transport of VEGF in an idealized microenvironment around a sprouting vessel. The above diagram, the base model, includes the processes of VEGF secretion and clearance (A), VEGF binding to sprout surface receptors (B), and VEGF binding to HSPGs and VEGF proteolysis in the interstitium (C). The domain is an axially-symmetric tissue cylinder, 160 μm in length and 50 μm in radius, selected to mimic in vivo sprout spacing. The model considers the isoforms VEGF₁₂₁, VEGF₁₆₅, and VEGF₁₈₉ in isolation to compare to single-isoform-expressing in vivo systems, and allows for cleavage of isoforms into VEGF₁₁₄, the MMP-cleavage product. Receptor signaling is modeled with the isoforms' interactions with VEGFR1, VEGFR2, and NRP1 (B). While the reactions are shown primarily for VEGF₁₆₅, isoforms VEGF₁₂₁ and VEGF₁₈₉, where bracketed, participate in similar reactions. VEGF and receptor-binding gradients are measured between the front and rear of the tip cell (indicated in gray arrowheads) (A). Extensions of this model explored here include gradients of HSPG and VEGF degradation (Figure 4).