Biomedical Engineering Reference
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environment in which the cells reside. The observed lower values can be partly
explained by the fact that the experiments are performed in a more realistic,
noisy environment, that reduces the persistence length of cell motion. More-
over, the cell takes 6 h to reach the opposite side of the chamber. In this
case, obviously, x CM (t = 6 h) = 300 m: this value is used as a reference
value.
Figure 6.7 also illustrates also the time course of the intracellular cal-
cium signals in two perpendicular sections of the cell. As reference sections we
choose the z = 2 vx ( 1 m) plane, which includes the development of the
pseudopodium, and the y = 100 vx ( 50 m) plane, the main transversal
section of the cell. After a short latency ( 30 min), surface receptor activa-
tion by VEGF stimulates the full activation of downstream cascade leading to
the subsequent production of second messengers AA and NO, which, in turn,
start to induce calcium influx from the extracellular environment through
the relative channels. The resulting intracellular calcium events, initiating at
the sub-plasma membrane regions, rapidly propagate in every direction, to
inhomogeneously fill the whole cell volume. The final pattern of Ca 2+ accu-
mulation is strongly localized: higher concentrations (> 2 M) occur in the
leading front of the polarized cell (i.e., at the tip of the pseudopodium), and
decay within a distance of 15{20 m (< 1 M). They are undetectable in the
peri-nuclear regions (< 0.5 M in the range (10 m, 30 m) of the cell x-cross
section). Moreover, the rate of the final intracellular accumulation of the ion
is c (t = 6 h) 3.6.
These findings are in agreement with both experimental [390] and model-
ing [283] data on the spatial propagation of calcium events in endothelial cells
stimulated with angiogenic factors. Indeed, as described in more detail in the
next chapter, the heterogeneity of accumulation of the ion is highly relevant
during the overall angiogenic progression, as several reports have suggested
that the transcriptional pattern of specific genes during vascular formation
critically depends on the spatiotemporal calcium dynamics [108, 130]. Finally,
if the external VEGF stimulus is subsequently removed, imposing S = 0, the
production of AA and NO ceases and they rapidly decay. The cytosolic cal-
cium, extruded by pumps and exchangers, then quickly returns to the baseline
level C 0 (not shown).
6.5 Interfering with Calcium Machinery
To establish a direct qualitative and quantitative relation between intracellular
calcium events and cell motion, in Figure 6.8, we study the consequences of a
gradual inhibition of the Ca 2+ influx distributions.
In particular, we decrease in a graded fashion the overall VEGF-induced
 
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