Biomedical Engineering Reference
In-Depth Information
FIGURE 6.3: Diagram of the key VEGF-induced intracellular Ca
2+
pro-
cesses included in the mathematical model. Cell surface receptors activated
by VEGF molecules stimulate the biosynthesis of AA and NO which, in turn,
mediate calcium entry from the extracellular environment into the cytosol.
Cytosolic Ca
2+
is reversibly buffered by proteins and extruded back from the
cell.
6.2.2 Molecular-Level Model
The key biochemical processes incorporated in the model of the VEGF-
induced calcium dynamics are as follows (see Figure 6.3 for a diagrammatic
representation):
The exogenous VEGF diffuses throughout the extracellular medium,
where it decays with a characteristic half-life.
Single molecules of the morphogen reversibly combine with their tyrosine
kinase receptors on the cell surface and form receptor{ligand complexes.
These complexes decompose into a free receptor (which is recycled back)
and some products, that initiate a sequence of reactions (i.e., the ac-
tivation of enzymes PLA2 and eNOS) culminating in the production
in the sub-plasmamembrane regions of second messengers AA and NO
[137, 211, 276, 390].
AA and NO open the relative and independent calcium channels in the
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