Figure 9

Summary of VEGF transport results. A, We propose that isoform-specific patterning in tissues results from differences in their rates of degradation (i.e. isoform-specific degradation), potentially mediated by HSPG or NRP1 binding. For longer isoforms to have more localized VEGF distributions [13], their degradation must be more rapid. We hypothesize that proteases enhance the spatial propagation of VEGF (i.e. VEGF redistribution) [16, 17, 19] by inhibiting this isoform-specific VEGF degradation. B, Role of matrix-binding affinity on VEGF patterning. Our computational model shows that HSPG-binding affinity affects soluble and matrix-bound VEGF in different manners. Increased matrix binding affinity universally decreases total soluble VEGF, in the case of HSPG-mediated isoform-specific degradation. However, matrix-bound VEGF shows increased "localization", a result of two competing behaviors: an increase in concentration due to accumulation close to the source of secretion, and a decrease in concentration farther away due to an increased rate of degradation. This causes matrix-bound VEGF to lose its isoform-monotonic behavior. The ordering of how isoforms are perceived is dependent upon the distance that sensing occurs from the VEGF source.