Biomedical Engineering Reference
In-Depth Information
8.5 Varying Cell Elasticity
We now turn to address how the invasiveness of the tumor changes as a func-
tion of
perimeter
;C
, that describes the degree of cell membrane elasticity (see
Figure 8.7). Small values of
perimeter
;C
allow the cells to reorganize their shape
more substantially and to traverse the extracellular matrix more readily. The
consequent enhancement of invasiveness is due to a distribution of the external
individuals, which, able to remodel their shape to adapt to the directions of
ECM protein gradients, can venture further from the main body of the mass,
as reproduced in Figure 8.7(A). At high values of
perimeter
;C
, a decrement of the
invasive distance instead occurs, as the malignant cells cannot reorganize and
expand eciently in their environment, even if they have an increased motil-
ity and the preference to heterophilic (i.e., cell{matrix) contacts; see Figure
8.7(B). Indeed, we can conclude that the ability of tumor cells to undergo con-
tinuous and dramatic changes in their morphology during motion has a big
impact on the aggressiveness of the disease, as also provided in [332]. A ther-
apeutic approach that targets the dynamics of polarization/depolarization of
the cytoskeletal of cancer cells, as the use of phalloidin-like compounds, may
be therefore potentially effective.
8.6 Altering Cell-Substrate Interactions
We finally analyze how the invasiveness of the tumor is influenced by the
haptotactic capacity related to the coecient
hapt
; see Figure 8.8(A). An in-
creased sensitivity of cells to ECM protein gradients prompts in fact the tumor
front to more significantly move in the extracellular environment, eventually
promoting invasion. On the contrary, low values of
hapt
results in an isotropic
movement of malignant individuals, which are therefore unable to maintain
directional persistence and to deeply penetrate in the host tissue.
The inhibition of cell haptotactic sensitivity can therefore represent a po-
tential ecient intervention strategy. In particular, it can be reproduced in
vitro by adding saturating amounts of matrix components, that extinguish
substrate inhomogeneities. In this regard, experimental evidence have demon-
strated that, consistently with our results, cells cultured in matrices with high
collagen densities show a dramatic downregulation of their migratory capac-
ity, driven by the fact that their integrin receptors are completely engaged
without maximal cell spreading and movement [123, 156].
An analogous behavior is seen by varying the cell proteolytic activity, mea-
sured by the parameter
p
; see Figure 8.8(B). In particular, low values of
p
translate into a partial degradation of ECM proteins; see Figure 8.8(C), whose
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