HGF-Induced Cell Scatter - Cellular Potts Models: Multiscale Extensions and Biological Applications - page 22

FIGURE 2.4: Comparison of the evolution in time of the Scattering Index
(as defined in Equation (2.3) of ARO cells for experimental (dark line) and
simulation (light line) evidences. Error bars show standard deviations over ten
representative colonies for the experiments and over ten simulations.

The evolution of the simulated colony compares well with the experimental
evidences, having also the same temporal dynamics, as shown in Figure 2.4,
where we plot the scattering index

S I (t) = A(t)

A(0) 1;

(2.3)

with A(t) defined as the area of the minimal convex polygon enclosing the
aggregate at time t and A(0) the one at t = 0. The experimental scatter begins
slightly slower than the simulated; however, after the initial phase (t > 1500
MCS), S I increases at comparable rates in both cases.
To further study the robustness of the model and to identify the critical
features of the output, we analyze how the results of the simulations depend
on the parameters by measuring the scattering index after 3000 MCS (i.e., 1
day). Figure 2.5 (left panel) shows that, at suitable T, our simulated aggre-
gates do not scatter for low values of intercellular adhesion parameter J C;C ,
corresponding to strong intercellular adhesion, whereas they dissociate when
cells adhere less strongly: this observation well corresponds with the exper-
iments where ARO aggregates scatter at high concentrations of HGF (see
[101]).
In the right panel of Figure 2.5, we also look for the motilities required for
the process: for T < 15, there is no detectable scattering within the time limit
(3000 MCS), independently of the adhesion energies J C;C (the cells dissociate,
but do not spread away), while for T > 60 they break up into small pieces or
fragments, a well-characterized nonbiological artifact of the CPM due to the