Biomedical Engineering Reference
In-Depth Information
or the middle structure indeed reflect the different overall phenotypes, i.e.,
invasive and permeative, respectively.
Finally, in the case of the smallest channel, the cell average velocity (obvi-
ously evaluated only for cells with an elastic nucleus) slightly decreases again
to less than 1 m/min. The explanation resides in the fact that although the
nucleus is deformable, it is however stiffer (and less motile) than the surround-
ing cytoplasm and therefore takes more time to remodel and move, slowing
the overall individual, as we will described below in greater detail.
These results first reveal two distinct migratory phenotypes that are pro-
posed to occur for cells placed either in open structures (i.e., 2D surfaces or
large channels) or in confined architectures (i.e., channels smaller than cellular
dimensions). In the first case, the movement of cells is widely independent of
their elastic properties, whereas it is widely known to strongly rely on their
adhesive strengths [225]. On the contrary, the ecacy of cell migration in
3D constrained environments is mainly determined by the deformation ability
of the moving individuals (in particular, of their voluminous nucleus), which
adapt to the geometrical characteristic of the environment. In this regard, it is
indeed possible to identify an optimal dimension of an extracellular structure
that results in sustained cell locomotion: smaller than the cellular measures
but higher than the nuclear diameter.
The drastic differences in cell migration speeds due to the specific environ-
ment dimensionality captured by the model are consistent with recent studies
performed on NIH-3T3 fibroblasts [110], leukocytes [225], and pancreatic can-
cer cells [332]. In these cases, the authors have in fact demonstrated that
cell movement in 3D confined structures is more rapid, uniaxial, and closely
dependent on cell morphological transitions. In striking contrast, the basic
program of cell migration over flat ECM substrates strongly requires a dy-
namical adhesion to their environment via adhesive molecules, i.e., integrins,
which generate the force necessary for propulsion and movement [7, 229].
Analogous conclusions have been found also by a theoretical model that has
reported that the migration of cells in a microsized channel strongly depends
on partial pressure differences formed between the channel walls and either
the leading or the rear edge of the individual, without the necessity of specific
cell-surface adhesion molecules [181].
10.5 Migration Modes
We finally investigate whether in the different cases cells display a specific
phenomenological/mechanical movement. In particular, in order to elucidate
if cell distinct parts show coordinated movement, we separately tracked the
leading edge, the nucleus, and the rear edge of the cells, and we plot their
absolute position inside a channel versus time in a 2-h span.
Search WWH ::
Custom Search