Wound Healing Assay - Cellular Potts Models: Multiscale Extensions and Biological Applications - page 78

The first set of simulations analyzes the healing capacity of the cell popu-
lation in the absence of HGF stimulation (i.e., imposing S(t) = 0 in Equation
(5.2)). The cultures displays barely no detectable invasion within the obser-
vation period (D(t = 12 h) 10%), which is indicative of the low basal
motility of cells, given by T 0 ; see Figure 5.3(A-C). In particular, unstimulated
individuals typically maintain close contacts with each other and feature a
negligible random-oriented movement. Such a behavior is summarized in the
polar plot in Figure 5.3(B), which represents the spatial distribution of their
net displacement: the isotropy of directions is easily recognized by observing
the circular shape of the delimited area of the chart, while its small size high-
lights the inability of cells to strongly move away from their starting point
and invade surrounding spaces. Coherently, as represented in the (D) panel
of the same figure, the instantaneous speed of the unstimulated cells tends to
remain stable around a low initial value during the whole simulation period.
The evolution of the unstimulated ARO culture coincides qualitatively well
with experimental evidence, as shown in the same figure and provided in [101].
This gives us confidence in the choice made for the parameters describing
the basal properties of the simulated AROs, in particular, for T 0 . Indeed,
in the light of these considerations, simulations of wound healing assays in
the case of unstimulated cell lines, along with comparisons with the relative
experimental counterparts, will be used in the following chapters as basic
migratory tests, which will allow one to infer the value of the intrinsic motility
of the populations of interest.
After the addition of nanomolar concentration of chemical, the cell popu-
lation is observed to have an evident enhancement of motility with the overall
movement biased toward the gap, which is significantly invaded, as D(t = 12
h) 40%; see Figure 5.4.
In order to focus on the differences in the behavior of single individuals
within the culture, we divide the cell mass into three regions from its front,
namely, external, middle, and internal, as illustrated in Figure 5.4(A). We
then consider the cells allocated to each color-coded region and analyze their
movement in time, comparing the resulting migratory parameters. We find
that the AROs placed at the edge of the scratch are characterized by a high
short-range motility, which overcomes their adhesive interactions and allows
them to shed; see Figure 5.5(A). In particular, as represented in the (B) panel
of the same figure, such external individuals typically move according to angles
that moderately cluster around the expected direction, i.e., the middle of the
wound, as shown by a good value of linearity (L 0.6).
The cells located in an intermediate position have instead decreased the
average net displacement and linearity, while those far away from the front
feature an almost negligible isotropic movement. As a further confirmation
of the different dynamics of the three subpopulations, the evolution of the
instantaneous speeds are reported in Figure 5.5(C): external cells move faster
than middle cells, and the velocity is significantly further reduced for internal
individuals. The migratory capabilities of cells therefore decrease with the