Biomedical Engineering Reference
In-Depth Information
FIGURE 1.4: Illustrative simulations of the biological role of the adhesive
energies. In a 200 200-site domain , a round cluster of cells is placed. The
cells are of two different types (i.e., light and dark), with initial and target
measures as in the previous case, as well as the values of
surface
L
=
surface
D
=
L
=
perimete
D
= 0:2 site
1
. The final configurations
correspond to J
L;D
= 0:4 J
L;L
= J
D;D
= 20 and J
L;M
= J
D;M
= 0 (left
panel); J
L;D
= 20 J
L;L
= J
D;D
= 0:2 and J
L;M
= J
D;M
= 0 (middle
panel); J
L;D
= 20 J
L;L
= J
D;D
= 0:2 and J
L;M
= 0:8 J
D;M
= 12 (right
panel).
and
perimeter
50 site
2
aggregate quickly dissociates into isolated individuals, displaying a scattered
phenotype. In fact, not only do external cells lose contact and spread away
from the main spheroid, but a repulsion occurs also among individuals within
its core, because for the cells it costs more to stay attached to each other than
to float in the medium (Figure 1.3 (right panel)).
As we will described more in detail in the following chapters, the disper-
sion of single cells upon low intercellular adhesion is of particular relevance
in the early stages of solid cancer growth and development. The malignant
individuals able to escape from the main tumor mass have in fact the greatest
invasive potential, as they can invade the host tissue and further metastasize.
In multicellular organisms, the relative adhesion of various cell types to
each other or to noncellular components surrounding them is also fundamen-
tal. From the late 1950s, it has been widely noticed that during embryonic
development the behavior of cell aggregates resembles that of viscous fluid. A
random mixture of two types of embryonic cells, in fact, spontaneously reor-
ganizes to reestablish coherent homogeneous tissues. A similar process is a key
step also in the regeneration of normal animal from aggregates of dissociated
cells of adult hydra. It also explains the layered structure of the embryonic
retina. These phenomena, commonly called cell sorting, involve neither cell
division nor differentiation, but are entirely caused by spatial rearrangements
of cell positions due to differences in the specific adhesivities; see [165, 169]
and references therein. Indeed, specific hierarchies of adhesive strengths lead
to specific configurations of the cellular aggregate.
The most famous simple and intuitive CPM simulation reproducing bi-
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