  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.
