The impact of high density receptor clusters on VEGF signaling

Ye Chen, Christopher Short, Adám M. Halász, Jeremy S. Edwards

Research output: Contribution to journalConference articlepeer-review

4 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF) signaling is involved in the process of blood vessel development and maintenance. Signaling is initiated by binding of the bivalent VEGF ligand to the membrane-bound receptors (VEGFR), which in turn stimulates receptor dimerization. Herein, we discuss experimental evidence that VEGF receptors localize in caveloae and other regions of the plasma membrane, and for other receptors, it has been shown that receptor clustering has an impact on dimerization and thus also on signaling. Overall, receptor clustering is part of a complex ecosystem of interactions and how receptor clustering impacts dimerization is not well understood. To address these questions, we have formulated the simplest possible model. We have postulated the existence of a single high affinity region in the cell membrane, which acts as a transient trap for receptors. We have defined an ODE model by introducing high- and low-density receptor variables and introduce the corresponding reactions from a realistic model of VEGF signal initiation. Finally, we use the model to investigate the relation between the degree of VEGFR concentration, ligand availability, and signaling. In conclusion, our simulation results provide a deeper understanding of the role of receptor clustering in cell signaling.

Original languageEnglish (US)
Pages (from-to)37-52
Number of pages16
JournalElectronic Proceedings in Theoretical Computer Science, EPTCS
Volume125
DOIs
StatePublished - Aug 27 2013
Externally publishedYes
Event2nd International Workshop on Hybrid Systems and Biology, HSB 2013 - Taormina, Italy
Duration: Sep 2 2013 → …

ASJC Scopus subject areas

  • Software

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