AUTHOR=Hashambhoy Yasmin L., Chappell John C., Peirce Shayn M., Bautch Victoria L., Mac Gabhann Feilim 

TITLE=Computational Modeling of Interacting VEGF and Soluble VEGF Receptor Concentration Gradients

JOURNAL=Frontiers in Physiology

VOLUME=volume 2 - 2011

YEAR=2011

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2011.00062

DOI=10.3389/fphys.2011.00062

ISSN=1664-042X

ABSTRACT=Experimental data indicates that soluble VEGF receptor 1 (sFlt-1) modulates the guidance cues provided to sprouting blood vessels by vascular endothelial growth factor-A (VEGF).  To better delineate the role of sFlt-1 in VEGF signaling, we have developed an experimentally-based computational model.  This model describes dynamic spatial transport of VEGF, and its binding to receptors Flt-1 and Flk-1, in a mouse embryonic stem cell model of vessel morphogenesis.  The model represents the local environment of a single blood vessel.  Our simulations predict that blood vessel secretion of sFlt-1 and increased local sFlt-1 sequestration of VEGF results in decreased VEGF-Flk-1 levels on the sprout surface.  In addition, the model predicts that sFlt-1 secretion increases the relative gradient of VEGF-Flk-1 along the sprout surface, which could alter endothelial cell perception of directionality cues.  We also show that the proximity of neighboring sprouts may alter VEGF gradients, VEGF-receptor binding, and the directionality of sprout growth.   As sprout distances decrease, the probability that the sprouts will move in divergent directions increases.  This model is a useful tool for determining how local sFlt-1 and VEGF gradients contribute to the spatial distribution of VEGF-receptor binding, and can be used in conjunction with experimental data to explore how multi-cellular interactions and relationships between local growth factor gradients drive angiogenesis.