Biomedical Engineering Reference
In-Depth Information
9.5.1
Design Concept of Engineered Micro-environments
The cell migration assay described above has identifi ed the functions of grooved
surfaces as cell repellant, a trap, and a fi lter of migrating cells. This section discusses
the mechanisms underlying cell response to the substrate topography and proposes a
design concept of the engineered microstructured surfaces with these functions.
9.5.1.1
Cell Repellent
In designing a cell repellent groove, the groove width is an important design
variable (Fig.
9.8a, c
).
In both L-W1.5 and IS-W1.5 grooves, after the leading lamella encounters the
front edge of the groove, the cell body moves straight until it bridges the groove
(Figs.
9.3d
and
9.6b
). In this fi rst process, the grooved surface will primarily work
as a foothold, not a repellent, for the cell to generate traction force to drag the
cell body into the groove. A similar effect of a narrow gap has been reported that a
cell migrating through a three-dimensional environment protrudes into small,
micro-scale gaps, and forms an anchoring site there to pull the cell body (Ghibaudo
et al.
2009
; Mandeville et al.
1997
).
In the next process of cell interaction with L-W1.5 and IS-W1.5 grooves
(Figs.
9.3d
and
9.6b
), the cell body stalls on the narrow grooves, probably due to
stiffness of the nucleus or the cytoplasm around it (Maniotis et al.
1997
; Dahl et al.
2008
). In the stalled cells, repositioning of cell nucleus, which is known to play an
important role in cell polarization (Gomes et al.
2005
), occurs. This is thought to be
responsible for the change in lamella protrusion in the backward direction.
Thus, to obtain effective repellents of migrating cells, it is necessary to design
grooves that are narrow and deep enough to work both as anchoring sites to pull the
cell body and also as obstacles to prevent the translocation of the cell nucleus into
the grooves.
9.5.1.2
Cell Trap
The cell trapping effect (Fig.
9.8d
) of the IS-W4 grooves is reliable and reproducible
for all the cells that once enter the grooved surface. On the surface with IS-W4
grooves, cellular protrusion is signifi cantly affected by the square pillars formed by
the intersecting grooves due to stable and preferential interaction of cells with the
pillars, and thus keratocytes changes their shape and are trapped (Fig.
9.6a
).
Fibroblasts migrating on the circle pillar surface with a specifi c dimension are
known to exhibit a more branched shape and less directional stability than those on
a fl at surface (Ghibaudo et al.
2009
; Frey et al.
2006
). Compared with fi broblasts
on a circle pillar surface, keratocytes on an intersecting grooved (square pillars)
surface seems to be more effectively-trapped, probably because of the difference in
cell type.
