Figure 4
Mechanisms of forming differential isoform gradients. We consider the distributions of VEGF121, VEGF165, and VEGF189 under four scenarios that may be responsible for isoform patterning in vivo (i, soluble fraction; ii, bound fraction; iii, soluble + bound VEGF). A, reversible HSPG binding considered previously in Figure 3 (HSPG-binding-only model). B, patterning of the underlying HSPG ([H]Total = 750 nM at z = 0, 30%/40 μm). C, soluble VEGF degradation; this is isoform-independent degradation (all isoforms are degraded at the same rate), but HSPG-bound VEGF is protected from degradation; kdeg = 10-3 s-1. D, matrix-sequestered VEGF degradation; all isoforms are degraded, and HSPG binding confers no protection; this has the effect of increasing degradation of HSPG-binding isoforms due to their longer residence time, even though all isoforms have the same degradation rate constant kdeg = 10-3 s-1.