Biomedical Engineering Reference
In-Depth Information
Protocols involving ROCK inhibitors for dissociated human ES cells and human
iPS cells have already improved a number of practical procedures (Ohgushi et al.
2010
; Watanabe et al.
2007
). A higher survival rate of human ES cells and human
iPS cells in dissociated culture is achieved by the inhibition of ROCK-dependent
hyperactivation of actomyosin (Ohgushi et al.
2010
; Watanabe et al.
2007
). The
degree of actin cytoskeletal tension mediated by ROCK plays a major role not only
in the stem cell survival rates but also in directing stem cell differentiation to a spe-
cifi c cell type and in retention of multipotency by stem cells (Table
11.1
) (McMurray
et al.
2011
).
Further studies of pathways and molecules involved in actin cytoskeleton-
mediated control of stem cell fate will open up new ways to develop synthetic ECM
for more sophisticated control of cell fates.
11.3
Modulation of Actin Cytoskeleton by Topographical
and Mechanical Cues from Extracellular Matrix
The physiological roles of actin cytoskeleton, which are explained in Sect.
11.2
,
indicate that modulation of actin cytoskeleton lead to control of cell function and
fate. This section describes basic knowledge in designing synthetic ECM to provide
topographical and mechanical cues for the modulation of actin cytoskeleton.
Cells
in vivo
mechanically as well as chemically interact with the extracellular
environment. As described in Sect.
11.2.2.1
, actin cytoskeleton plays a central role
for cells in order to sense, integrate, transduce, and respond to the physical cues
provided by ECM niche. Vice versa, a synthetic ECM niche engineered as a source
of mechanical cues is expected to be effective at modulation of the actin cytoskele-
ton. Especially, ECM topographical and mechanical features signifi cantly modulate
actin cytoskeleton.
11.3.1
Topographical Cue
A key concept in designing topographical cue is that topographical features of ECM
serve as structural constraints at several scales. The features tens of micrometers in
size act directly on a single cell or cells in a cell population (Sect.
11.3.1.2
). The
features sub-micrometers to ten micrometers in size act on the actin cytoskeleton
(Sect.
11.3.1.3
), whereas features ten to hundreds of nanometers in size act on inte-
grin molecules (Sect.
11.3.1.4
). These structural constraints affect the shape of the
cell-ECM interface and affect the mechanical homeostasis between the cell and
ECM (Schwartz and Chen
2013
); this process leads to actin remodeling through
downward and upward causation (Miyoshi and Adachi
2012
) in the mechanochemi-
cal interactions between factors of different size levels.
