Biomedical Engineering Reference
In-Depth Information
FIGURE 2.5: Dissociation process in response of HGF in a culture of ARO
cells. The scattering index at t = 3000 MCS, defined as (2.3), as a function of
(left panel) cell{cell adhesion energy J
C;C
at T = 20, T = 30, T = 40, T = 50
and T = 60 and of (right panel) Boltzmann temperature T at J
C;C
= 10,
J
C;C
= 30, J
C;C
= 50 and J
C;C
= 70. Error bars show s.d. over 10 simulations.
fact that too high agitation rates result in a chaotic sequence of spin flips [260]
(not shown). For the in-range values (i.e., 30 < T < 60), the process becomes
more significant and quicker for every T-increment.
These results validate our hypothesis that HGF concentration can be mod-
eled by increasing simultaneously T and J
C;C
, since both an enhancement in
cell motility and the breakage in E-cadherin bonds are needed for ARO cell
scattering, as seen in experiments. In particular, such distinctive effects of
HGF on ARO cells are clearly detected at a certain range of doses (i.e., in
a certain range of model parameters), since they are not elicited for lower
quantities. Therefore, it can be concluded that the ARO cells acquire not only
an HGF-dependent phenotype but an HGF dose-dependent one.
Figure 2.6 shows a definitive confirmation of the HGF-induced increase
of cell motility, comparing the single-cell trajectories during a 24 h (= 3000
MCS) time-lapse, both in the control and in the stimulated case resulting from
the experiment and the numerical simulation: the value of the mean effective
distance covered by an ARO cell is about 5 m in the absence and 12 m in
the presence of the growth factor (the mean is over ten representative cells,
with a standard deviation of 1 m in both cases), which conrms that,
under normal conditions, ARO cells are characterized by a virtual nonmotile
phenotype.
The enhancement of cell motility and dissociation can be further captured
by a wound healing assay. This experimental model tests, in fact, the ability
of a cell line to fill gaps created in cell monolayers and is generally considered
a simple and reliable test for quantitative evaluation of cell migratory pheno-
type. Indeed, a confluent monolayer of ARO cells, grown in fetal calf serum,
Search WWH ::
Custom Search