Biomedical Engineering Reference
In-Depth Information
FIGURE 3.5: The initial condition of simulated single tumor cell mesothelial
invasion and description of the symbols used in the model.
biological effect, a lattice site x within an ECM molecule becomes a generalized
pixel of medium when the local level of MMPs (m(x;t)) is suciently high
(i.e., > 2.5). This change is implemented by changing (
(
x
)
) from E to F.
3.3 Single Cell Transmigration
The in vitro transmesothelial migration of a single ovarian cancer cell is mod-
eled in a two-dimensional 162 px 50 px section illustrated in Figure 3.5 (
162 m 50 m, since in our lattice 1 px corresponds to 1 m), where the
border at the bottom is the virtual Petri dish, as seen labeled with = S. The
mesothelial layer is formed by 27 px 9 px rectangular cells ( = M), and
surrounded by a sort of pericellular matrix made up for ECM bers ( = E).
The area between the simulated mesothelium and the dish is a mixture of
interstitial uid ( = F) and ECM molecules ( = E again), that mimics
the experimental sub-mesothelial-type matrigel used to anchor the monolayer.
The virtual ECM components are arranged in random lines, representing fiber
bundles. The round cancer cell ( = C), with a diameter of 14 px, is placed
in proximity of the layer, within the peritoneal uid (again = F).
The overall simulation lasts 1200 MCS, which, fitting the experimental
times, we set to correspond to about 5 h, dening 1 MCS 15 s. As outlined in
the experiments, the mesothelial cells, anchored to fixed and rigid ECM fibers,
form a continuous and stable pavement and barely move from their original
position, maintaining their characteristic shape. Conversely, the tumor cell is
subjected to dramatic surface and volume alterations and remodeling, since
it has the ability to spread on and to suddenly cross the monolayer through
gaps created by the retraction of mesothelial cells. These considerations lead
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