Biomedical Engineering Reference
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FIGURE 2.2: Typical time sequence of in vitro branching morphogenesis of
a colony of MLP-29 cells, incubated for 24 h in DMEM - 1% FCS, containing
recombinant hepatocyte growth factor (HGF), diluted to the final concentra-
tion of 100 ng/mL, at 1 h, 6 h, 10 h, 15 h, 20 h, and 24 h after incubation.
The scale bar is 25 m long.
compact aggregates of undifferentiated, almost round cells, with the interstitial
spaces almost filled with microvilli protruding from the cell surface along the
entire perimeter of each cell [271].
In HGF-driven scattering, the cells in the middle of an island do not un-
dergo a dramatic change of shape, keeping their original elliptical shape, and
passively move only when dragged by the nearest sprout. On the other hand,
the cells at the margin acquire a polar configuration driven by a cytoskeletal
remodeling: they become highly asymmetric and have distinct apical, lateral,
and basal surfaces that correspond to a leading and trailing surface during
their migration. In particular, they migrate faster along their long axes than
along their short axes: such an anisotropic, cell-shape-dependent motility re-
sults in strong directional persistence because the cells must reorient before
moving toward a new direction and also introduces two timescales into scat-
tering: fast migration along the cells' long axes produces rapid branching and
polarization, whereas the slower sideways migration coarsens the pattern as
the cells align and close small lacunae. The polarized cells, in the part of their
surface in contact with the ECM, extend filopodia toward the open space and
keep a thin adhesion point with the main corpus of the colony.
The branches, generally formed by couples of parallel elongated cells, are
radially disposed with angles ranging between 15 and 100 degrees. If the HGF
is no longer added to the culture, it can be observed as a sort of involution of
the sprouts, and the colonies tend to become round and compact again (not
shown).
2.2 Mathematical Model for ARO Aggregates
The scattering process is modeled on a bidimensional domain , which is
consistent with the planar substrates used in the experiments. The ARO indi-
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