Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradients
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....
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doaj-8d944f362f994fd0ac0a60bbcbf223172020-11-24T21:18:17ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2011-10-01210.3389/fphys.2011.0006210062Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradientsYasmin L Hashambhoy0Yasmin L Hashambhoy1John C Chappell2John C Chappell3Shayn M Peirce4Victoria L Bautch5Victoria L Bautch6Victoria L Bautch7Feilim eMac Gabhann8Feilim eMac Gabhann9Johns Hopkins UniversityJohns Hopkins UniversityThe University of North Carolina at Chapel HillThe University of North Carolina at Chapel HillUniversity of VirginiaThe University of North Carolina at Chapel HillThe University of North Carolina at Chapel HillThe University of North Carolina at Chapel HillJohns Hopkins UniversityJohns Hopkins UniversityExperimental 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.http://journal.frontiersin.org/Journal/10.3389/fphys.2011.00062/fullDevelopmental Biologycomputational modelmathematical modelVEGFAngiogenesisVascular Development |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yasmin L Hashambhoy Yasmin L Hashambhoy John C Chappell John C Chappell Shayn M Peirce Victoria L Bautch Victoria L Bautch Victoria L Bautch Feilim eMac Gabhann Feilim eMac Gabhann |
spellingShingle |
Yasmin L Hashambhoy Yasmin L Hashambhoy John C Chappell John C Chappell Shayn M Peirce Victoria L Bautch Victoria L Bautch Victoria L Bautch Feilim eMac Gabhann Feilim eMac Gabhann Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradients Frontiers in Physiology Developmental Biology computational model mathematical model VEGF Angiogenesis Vascular Development |
author_facet |
Yasmin L Hashambhoy Yasmin L Hashambhoy John C Chappell John C Chappell Shayn M Peirce Victoria L Bautch Victoria L Bautch Victoria L Bautch Feilim eMac Gabhann Feilim eMac Gabhann |
author_sort |
Yasmin L Hashambhoy |
title |
Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradients |
title_short |
Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradients |
title_full |
Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradients |
title_fullStr |
Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradients |
title_full_unstemmed |
Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradients |
title_sort |
computational modeling of interacting vegf and soluble vegf receptor concentration gradients |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2011-10-01 |
description |
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. |
topic |
Developmental Biology computational model mathematical model VEGF Angiogenesis Vascular Development |
url |
http://journal.frontiersin.org/Journal/10.3389/fphys.2011.00062/full |
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