A computational analysis of in vivo VEGFR activation by multiple co-expressed ligands
Fig 1
Schematics of molecular detail and structure of multi-scale computational model.
(A) Whole-body compartmental model structure and mass flow. VEGF and PlGF are secreted from parenchymal cells, and sR1 is secreted by endothelial cells into the tissue interstitial space. Ligands and sR1 can then bind to EC receptors (leading to internalization and degradation), and can be transported between the tissue and blood via bi-directional vascular permeability or lymphatic draining of tissues into the circulation. Soluble species in the blood can be directly cleared from the blood. (B) Molecular interactions in tissue interstitial space between VEGF121, VEGF165, VEGF189, PlGF1, PlGF2, NRP1, sR1, and extracellular HSPGs/GAGs (M). It is assumed that, similar to NRP1-VEGFR1 complexes, VEGF121 and PlGF1 can bind to sR1-M. ECM-bound VEGF165, VEGF189, and PlGF2 can also bind to sR1. (C) Trafficking processes simulated in endothelial cells. (D) Site-specific phosphorylation and dephosphorylation of VEGFR2. (E) Abluminal (tissue-side) endothelial cell-surface molecular interactions between VEGF121, VEGF165, VEGF189, PlGF1, PlGF2, VEGFR1, VEGFR2, NRP1, sR1, and extracellular HSPGs/GAGs in the endothelial basement membrane (EBM).