Cell Migration in Engineered Microstructured Surfaces - Innovative Approaches to Cell Biomechanics - page 150

the balance (Okeyo et al. 2010 ) of the adhesive, protrusive, and contractile forces,
and causes the cell to be steered toward the flat surface (Fig. 10.5b , 160-280 s). A
likely mechanism for changing the force balance is illustrated at the bottom of
Fig. 10.8b . The contact guidance (the green arrows) for one side of the lamella
coupled with the lamellar protrusion (the light red arrows) on the flat surface
increase the tension in the direction between the lateral edges of the cell, and sub-
sequently, the increased tension (the dark gray arrow) suppresses the protrusive
activity (indicated by the red shade area) perpendicular to the tension but does not
affect the lamellar protrusion parallel to the tension (Kolega 1986 ). This causes the
lamellar protrusion to be restricted in the direction away from the grooved surface,
resulting in the cell being repelled by the grooved surface.

10.6.4 Mechanism of Cell Polarity Change

Previous studies have suggested that decreasing groove width or spacing corre-
sponds to increasing contact guidance (Lim and Donahue 2007 ; Flemming et al.
1999 ). Consistently, the guidance effectiveness of each groove constituting the
intersecting grooves is expected to increase with decreasing the groove width in
Fig. 10.6a . Contrary to our expectation, the intersecting narrow ( w ≤ 2 ʼm) grooves
repelled cells regardless of the angle of approach.
The repelling effect of narrower grooves on cells with a lower angle of approach can
be explained by the same mechanism as that for wider intersecting grooves (Fig. 10.8b ),
i.e., lamellar protrusion is restricted in the direction away from the grooved surface due
to increased tension in the direction between the lateral edges of the cell.
Regarding the cells with a higher angle of approach, just after the cells encounter
the grooved surface, the contact guidance works for preferential lamella protrusions
into the grooved surface because the cell body moves onto the grooved surface.
However, as suggested in Fig. 9.6b in Chap. 9 , the cell body stalls on narrow
grooves, probably due to stiffness around the cytoplasm of the nucleus or the nucleus
itself, and the repositioning of the nucleus, which is known to play an important role
in cell polarization, is probably responsible for the change in lamella protrusion in
a backward direction. This hypothesis is also supported by the results shown in
Fig. 10.7b in which the effect of narrow grooves ( w = 1 ʼm) to repel cells with a
higher angle of approach remains unchanged from a smaller spacing ( s = 3 ʼm) to a
larger spacing ( s = 15 ʼm).

10.6.5 Label Free Cell Separation Utilizing Biophysical

Interaction Between a Cell and Extracellular Matrix

Taken together with the results of cell migration assay, the basis of cell motility-
based filtering by the intersecting grooves is lies primarily on the lamellar dragging
effect resulting from contact guidance. If the lamellar dragging effect is tuned to be