Biomedical Engineering Reference
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lithographic and microprinting techniques have shown that the microstruc-
tural contact guidance not only affects cell migration, but also intracellular
functions [46, 120, 232]. Lastly, in vivo intravital imaging studies of carcinoma
cells in the mammary fat pad have pointed out the preferential chemotactic
movement of invasive malignant cells along thick bundles of collagen fibers
offering a 2D surface toward blood vessels [93], while in the lymph node para-
cortex, the aligned microarchitecture of collagen and fibronectin fibers en-
sheathed by fibroblastic reticular cells significantly influenced the migratory
behavior of T-cells [19] .
9.5 Varying Fiber Density
Turning to the question of how the matrix topological structure affects cell
migration in both two and three dimensions, we consider the effect of varying
the density of the fibrous component of the substrate.
The cell population is therefore planted in lattices with an increasing num-
ber of collagen-like fibers, isotropically disposed as in the standard cases of
Figure 9.1. In particular, in 2D, it means simulating migration over a sur-
face containing an increasing amount of matrix fibers distributed equally and
isotropically along the x and ydirections. Indeed, migration eciencies
develop a bell-shaped distribution from low toward high fiber numbers with
a maximum at intermediate fiber numbers (Figures 9.4, 9.5, and 9.6). At
low numbers of threads, the planar matrix is unsaturated and unpercolated
and cells are found to have a short-range movement. Without finding enough
collagen-like sites to attach at and to use for traction and significant displace-
ment, they in fact fluctuate in the interstitial medium around their initial
position. Indeed, the body of cells remains mainly round, regardless of their
deformation ability. The distance from the nearest matrix fiber is in fact too
high to for adhesive interactions; see Figures 9.5, and 9.6, bottom{right panels.
Increments in the number of bundles cause a progressive enhancement in
cell migratory behavior. In particular, an optimal topology of the collagenous
network (i.e., interfiber measure in 2D and pore dimensions in 3D) allows cells
to eciently move in the matrix environments. The specific distribution and
distance of matrix threads results, in fact, in an effective contact guidance
for moving individuals, which are forced to undergo a change in their shape
toward a more motile mesenchymal morphology, exerting the maximal inten-
sity of adhesive and traction forces needed for their motion. In particular, cell
spreading is isotropic, as the homogenous geometry of the fiber networks does
not lead to cell elongation in a preferential direction, as reproduced again in
Figures 9.5 and 9.6, bottom{right panels and in the insets therein.
At the higher number of bundles, the extent of cell movement substantially
decreases again in both 2D and 3D. However, the underlying biomechanical
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