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Multi-physics interactions drive VEGFR2 relocation on endothelial cells

Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) is a pro-angiogenic receptor, expressed on endothelial cells (ECs). Although biochemical pathways that follow the VEGFR2 activation are well established, knowledge about the dynamics of receptors on the plasma membrane remains limited. Ligand st...

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Autores principales: Damioli, Valentina, Salvadori, Alberto, Beretta, Gian Paolo, Ravelli, Cosetta, Mitola, Stefania
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711959/
https://www.ncbi.nlm.nih.gov/pubmed/29196628
http://dx.doi.org/10.1038/s41598-017-16786-4
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author Damioli, Valentina
Salvadori, Alberto
Beretta, Gian Paolo
Ravelli, Cosetta
Mitola, Stefania
author_facet Damioli, Valentina
Salvadori, Alberto
Beretta, Gian Paolo
Ravelli, Cosetta
Mitola, Stefania
author_sort Damioli, Valentina
collection PubMed
description Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) is a pro-angiogenic receptor, expressed on endothelial cells (ECs). Although biochemical pathways that follow the VEGFR2 activation are well established, knowledge about the dynamics of receptors on the plasma membrane remains limited. Ligand stimulation induces the polarization of ECs and the relocation of VEGFR2, either in cell protrusions or in the basal aspect in cells plated on ligand-enriched extracellular matrix (ECM). We develop a mathematical model in order to simulate the relocation of VEGFR2 on the cell membrane during the mechanical adhesion of cells onto a ligand-enriched substrate. Co-designing the in vitro experiments with the simulations allows identifying three phases of the receptor dynamics, which are controlled respectively by the high chemical reaction rate, by the mechanical deformation rate, and by the diffusion of free receptors on the membrane. The identification of the laws that regulate receptor polarization opens new perspectives toward developing innovative anti-angiogenic strategies through the modulation of EC activation.
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spelling pubmed-57119592017-12-06 Multi-physics interactions drive VEGFR2 relocation on endothelial cells Damioli, Valentina Salvadori, Alberto Beretta, Gian Paolo Ravelli, Cosetta Mitola, Stefania Sci Rep Article Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) is a pro-angiogenic receptor, expressed on endothelial cells (ECs). Although biochemical pathways that follow the VEGFR2 activation are well established, knowledge about the dynamics of receptors on the plasma membrane remains limited. Ligand stimulation induces the polarization of ECs and the relocation of VEGFR2, either in cell protrusions or in the basal aspect in cells plated on ligand-enriched extracellular matrix (ECM). We develop a mathematical model in order to simulate the relocation of VEGFR2 on the cell membrane during the mechanical adhesion of cells onto a ligand-enriched substrate. Co-designing the in vitro experiments with the simulations allows identifying three phases of the receptor dynamics, which are controlled respectively by the high chemical reaction rate, by the mechanical deformation rate, and by the diffusion of free receptors on the membrane. The identification of the laws that regulate receptor polarization opens new perspectives toward developing innovative anti-angiogenic strategies through the modulation of EC activation. Nature Publishing Group UK 2017-12-01 /pmc/articles/PMC5711959/ /pubmed/29196628 http://dx.doi.org/10.1038/s41598-017-16786-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Damioli, Valentina
Salvadori, Alberto
Beretta, Gian Paolo
Ravelli, Cosetta
Mitola, Stefania
Multi-physics interactions drive VEGFR2 relocation on endothelial cells
title Multi-physics interactions drive VEGFR2 relocation on endothelial cells
title_full Multi-physics interactions drive VEGFR2 relocation on endothelial cells
title_fullStr Multi-physics interactions drive VEGFR2 relocation on endothelial cells
title_full_unstemmed Multi-physics interactions drive VEGFR2 relocation on endothelial cells
title_short Multi-physics interactions drive VEGFR2 relocation on endothelial cells
title_sort multi-physics interactions drive vegfr2 relocation on endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711959/
https://www.ncbi.nlm.nih.gov/pubmed/29196628
http://dx.doi.org/10.1038/s41598-017-16786-4
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