Biomedical Engineering Reference
In-Depth Information
decreases to the intermediate range, though the cell morphology looks similar
to the previous case, the nuclear elasticity provides a further facilitation for
the movement of the entire individual. In fact, the number of permeative cells
increases. This is due to both the fact that moving cells can now more eas-
ily and more quickly pass through the channel entrance (the so-called entry
time, i.e., the time span from the first contact of the cell with the channel
to the moment when the whole cell body is completely inside it, decreases
[230]) and to the fact that they can more eciently migrate within its walls;
also their voluminous nuclear region is, in fact, able to assume a more elon-
gated and \mobile" conguration; see Figure 10.4(A, bottom panel). Finally,
the enhancement in nucleus elasticity results in a significant change in the
migratory phenotype of the cells in the smallest channel, as now half of them
can invade the structure. This change in the motile behavior is the obvious
consequence of the fact that cells are now able to compress and pull their nu-
clear region within the confined environment, as represented in Figure 10.4(A,
bottom panel) and (C).
The computational findings are supported by a number of experimental
approaches. In [27], glioma cell lines have been shown to squeeze through nar-
row locations in a brain model in vivo, thereby increasing their metastatic
potential, by significantly compressing their nucleus upon recruitment of non-
muscle myosin II (NMMII). Moreover, very recently, other authors have been
shown that the directional persistence of cancer cells in microsized structures
is mainly regulated by the steric hindrance due to the presence of a rigid and
voluminous nucleus [197, 198]. In particular, in [28, 332], Panc-1 cells have
been shown to overcome size exclusion in microchannels architectures upon
treatments with bioactive SPC. Finally, in [230], the authors have demon-
strated that the number of acute promyelocytic leukemia (APL) cells able to
migrate through lters of 5 m (i.e., smaller than cell diameters) signicantly
reduced upon exposition to paclitaxel, which stabilizes the intracellular mi-
crotubule network. Analogous results have been provided therein also with
primary human neutrophils moving in 3{m-size pores.
10.4 Migration Velocities
In Figure 10.5, we analyze the average velocity (v
, defined as in Equation
(1.13)), both on the flat surface and within the different channel structures.
This comparison allows one to elucidate and to further quantify the differences
between cell migratory phenotypes in specific geometric conditions. The ran-
dom movement of rigid cells on the planar substrate is characterized by a low
0.4 m/min-speed, which slightly increases for individuals with a deformable
cytoplasm, reaching almost 0.6 m/min. Indeed, there is no further variation
upon the enhancement of the nuclear compressibility. An analogous behavior,
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