Biomedical Engineering Reference
In-Depth Information
system [172]. Notable, more aggressive and metastatic cancer cells have been
recently shown to have a significant compliance with respect to nonmetastatic
individuals, which remain stuck at the vessel walls or when crossing the en-
dothelium and therefore are forced to be confined in the primary site.
For these reasons, a quantitative assessment of cell deformability has the
potential to be of significant value for diagnostic purposes, such as screening
and cancer grading, and for a more detailed prediction of the course of the
disease in individual patients [347]: indeed, it has given rise to a number of in
vitro models. For instance, 3D lattices consisting of reconstituted fibrillar col-
lagen are typically used to study cell migration in structures mimicking highly
confined in vivo connective tissues [409]. However, in most cases, these bioengi-
neered scaffolds lack well-controlled spatial characteristics, because small and
large pores results from the stochastic fiber polymerization processes, therefore
failing to recreate defined trails and barriers [122, 319, 409]. Indeed, specific
mechanisms of reassembly of fibrillar matrices have been recently combined
with microlaser procedures able to generate predefined tracks that create spa-
tially defined patterns of connective tissue organizations [196]. In this regard,
geometrical characteristics of 3D matrix environments can be easily controlled
and modulated also with migration assays whose key features are micro-sized
channel structures [197, 332].
Such different types of experimental systems are here reproduced and simu-
lated by the extended compartmentalized CPM. The method is used to extract
the main features of tumor cell invasiveness by working with a 3D channel en-
vironment. As an outcome, we focus on the experimentally addressable char-
acteristics of cell locomotion, i.e., overall displacement and velocity, predicting
how these quantities are influenced by manipulations either of the geometri-
cal features of the channels, or of the biophysical properties (i.e., elasticity)
of the cells themselves. We then use the simulated migration chip to com-
pare the migration of cells inside the microchannels and their movement on
a 2D flat surface, like the one located before the entrance of the channels.
Consistently with experimental observations on different tumor cell lines, our
approach allows one to discern the effect of the mechanical rigidity of each
cell compartment (i.e., the nucleus and the cytosolic region) in the migration
capacity of the entire individual. Moreover, our findings provide evidence of
the facts that migration characteristics of cells are very different in 2D and in
highly constrained 3D environments and that even the underlying dynamics
change.
10.2 Mathematical Model
The model of the microchannel device is analogous to the one presented in
the previous chapter.
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