A computational analysis of in vivo VEGFR activation by multiple co-expressed ligands
(A-C) Changes in free ligand levels in tissue interstitial fluid (A), EC surface VEGFR1 ligation and VEGFR2 phosphorylation (B), and the breakdown of VEGF and PlGF bound to EC surface VEGFR1 (C), in response to varying PlGF production. Quantities shown are normalized to baseline cases. (D-F) Effect of endothelial basement membrane (EBM) binding site density on EBM site occupancy (D), fraction of occupied EBM sites bound to different ligands and receptors (E), and VEGFR1 and VEGFR2 ligation by immobilized VEGF or PlGF (F). (G-I) Total activation of VEGFR1 and VEGFR2 (G), and break-down of relative ligation by each VEGF and PlGF isoform (H-I) with varying sR1 production.