Cell Migration in Engineered Microstructured Surfaces - Innovative Approaches to Cell Biomechanics - page 136

Regulation of cellular functions by ECM topographical and mechanical
properties is biologically non-invasive because it does not involve the use of chemi-
cals that sometimes interfere with cellular functions. Therefore, potentially, this
method can reduce side effects due to toxicity by exogenous chemical factors, as
well as immune rejection in biochemical and biological agents (Lim and Donahue
2007 ; Kim et al. 2009a ; Patel et al. 2010 ; Dalby et al. 2007 ; McMurray et al. 2011 ).
Of the physical properties of the ECM, surface topographical feature is an impor-
tant factor in designing biomaterials. It has long been recognized that surface topo-
graphical features ranging from several tens of nanometers to a few hundred
micrometers significantly affect cell motile behaviors (Lim and Donahue 2007 ;
Flemming et al. 1999 ; Curtis and Wilkinson 1997 ). For instance, micrometer and
sub-micrometer grooves are reported to be simple and effective surface models for
cell migration control (Flemming et al. 1999 ). In particular, it has been shown that
various types of cells, both embryonic (Curtis and Wilkinson 1997 ; Kurpinski et al.
2006 ) and somatic cells (Kim et al. 2009a ; Clark et al. 1990 ; Tan and Saltzman
2002 ; Hu et al. 2005 ; Uttayarat et al. 2005 ; Fraser et al. 2008 ), orient and migrate
predominantly along the direction of the longer axis of multiple parallel grooves.
In Chap. 9 , we mentioned a new design concept of cell repelling and trapping sur-
faces based on the analysis of the transient change in the behavior of highly migratory
cells approaching a grooved surface from a flat surface. The analysis demonstrates the
possibility that a filtering process occurs, leading to repelling or trapping. The finding
suggests that it is possible to develop a grooved surface for more elaborate control of
cell migration beyond rectifying cell migration along the longer axis of the grooves.
In this chapter, we describe the effect of topographical features of ECM on cell
migration and the design principles of a grooved surface with cell filtering based on cell
motility. We demonstrate the cellular properties that are crucial in determining whether
a cell is trapped or repelled, and the design variables of the grooved surface that are
important for motility-based cell filtering. Specifically, we show the results of a system-
atic analysis of cell behavior from a flat surface to a grooved surface by using test sub-
strates with microgrooves of various widths and spacings. The analysis demonstrates
that the subcellular sized intersecting grooves, which allow a cell to experience multiple
grooves, repel or absorb cells precisely according to the angle of approach of the cells
to the boundary with the grooved surface. The findings provide an insight on the inter-
action between cells and ECM, and further form a basis for label-free detection of target
cells as well as noninvasive control of cell migration on the surface of biomaterials.

10.2 Micro-/Nano-architecture of Extracellular Matrix

in Tissues

Cells in vivo experience various micro-/nano-architecture of the extracellular envi-
ronment. Cells sense, transduce, and integrate these physical inputs to adaptively
change their migratory behavior, whether individually through amoeboid or mesen-
chymal modes, or collectively (Friedl and Wolf 2010 ). Topography and stiffness are