Biomedical Engineering Reference
In-Depth Information
FIGURE 7.13: (See color insert.) Inhibition of network organization by dis-
rupting cell chemotactic response (i.e., imposing ch ;C = 0 for each in Equa-
tion (6.2). In panel (A), we observe the formation of poorly differentiated
vascular islands. As usually, the initial cell number is n = 150 while all the
other model parameters are the same of the basic simulation in Figure 7.3.
Scale bar is 100 m long. Panel (B) reproduces the magnication of four
representative single-TEC motion trajectories obtained from the time-lapse
simulation. The initial (i.e., at 0 h) position of individuals is labeled with 1,
while the final (i.e., at 12 h) with 2. Each segment tracks a displacement of
2 h. In the background the concentration field of VEGF is pseudocolor-scaled
so that the maximum level is red and minimum level is blue, as in Figure 7.6.
The motion of cells is uncorrelated from the directions of high VEGF concen-
tration, as they do not experience the chemical force. Moreover, in the absence
of the chemotactic stimulus, the individuals do not elongate, remaining in a
stationary un-polarized morphology.
Analogous results are observed with the direct exclusion of the cell direc-
tional persistence ( pers = 0 for all cells in Equation (6.4)), which is counter-
intuitive and currently hard to experimentally handle. The formed sprouts
are again immature and swollen. They are typically thick (3{4 cells wide) and
characterized by large intervascular spaces and by lT T 0.27L T and pct =
0.73, as depicted in Figure 7.12(B).
A further trivial, but possible, anti-angiogenic strategy deals with the in-
terference in the cell adhesive strengths. In particular, a high spatially ho-
mogeneous value of J ext
E;E is the computational counterpart of the function of
anti-VE-cadherin antibodies, which block VE-cadherin receptors preventing
the formation of contact junctions between cells. This intervention produces
aggregates of dispersed TECs, which are located in the zones of higher VEGF
concentrations (lT T 0.06L T , pct = 0.94), as reproduced in Figure 7.12(C).
Another strategy of high interest is the disruption of the chemotactic
 
Search WWH ::




Custom Search