Multi-physics interactions drive VEGFR2 relocation on endothelial cells

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 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Scientific Reports Springer Journals

Multi-physics interactions drive VEGFR2 relocation on endothelial cells

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Publisher
Nature Publishing Group UK
Copyright
Copyright © 2017 by The Author(s)
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
eISSN
2045-2322
D.O.I.
10.1038/s41598-017-16786-4
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Scientific ReportsSpringer Journals

Published: Dec 1, 2017

References

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