Biomedical Engineering Reference
In-Depth Information
6.7 Varying the Chemical Source
When the external chemical signal is extended to the whole right lower edge
of the migration chamber, with the same intensity
v
, we observe a different
cell shape reorganization; see Figure 6.14(A). After an initial stage ( 1 h),
in which its phenomenology resembles the standard case in Figure 6.6, the
motile TEC adapts to the new VEGF profile, featuring a flat and thin (
2 m) lamella in the direction of motion. An interesting consideration that
emerges here is that such a different morphological transition is completely
self-generating, and only due to the new spatial profile of the external stim-
ulus as, beside the extension of the VEGF source, we have not changed any
other model assumptions. The mechanical explanation is that, as reproduced
in Figure 6.15(A), the planar chemical source results in a planar front of
maximal concentration, which chemotactially stimulates a larger part of the
cell membrane to protrude, thus forming the flat lamella. On the opposite,
the standard VEGF point source features a curved profile: consequently, the
maximal chemical force, given by the maximal chemical gradient, is concen-
trated on a restricted part of the cell leading surface, from which the thin
pseudopodium emerges; see Figure 6.15(B).
A further confirmation of this mechanism is given by the fact that, at the
beginning of both simulations, when the curvature effects are not so strong,
the morphology of the cell is very similar. As far as we know, there are no in
vitro evidences replicating such a model outcome, probably because it is very
dicult to experimentally vary the local spatial extension of a chemical source.
However, this result is supported by plausible biomechanical implications. Ex-
ternal chemical signals are in fact demonstrated to be locally transmitted from
membrane-bound receptors to the nearest \central nodes" of cell cytoskeleton,
including small G-proteins Cdc42, Rac and Rho [180, 149, 388]. The activity of
the rho-family molecules, in turn, directly drives actin dynamics, regulating
and fine-tuning polimerization and nucleation processes of cytoskeletal fila-
ments, which determine the remodeling of the cytosol and the protrusion of
the plasma-membrane [125, 258, 293]. An extended (i.e., not punctual) exoge-
nous signal may therefore cause the growth of the actin filament network in
a larger part of the cell leading front, eventually resulting in the formation of
a flat motility structure, as the lamella emerged in our simulations. Interest-
ingly, as shown in Figure 6.14, the evolution of the cell migratory properties
(the overall displacement, as x
CM
(t = 6 h) = 300 m, and the directional
velocity) remains almost unaltered with respect to the standard case as well
as the VEGF-induced calcium dynamics. In particular, the peak of maximal
calcium response, that remains localized in the thinner part of the cell (in the
lamellipodium), measures 2.2 M, while c
(t = 6 h) 3.4. This considera-
tion provides the fact that proangiogenic Ca
2+
signals are typically localized in
the motility structures (either pseudopodia or lamellipodia) of vascular cells:
Search WWH ::
Custom Search