Biomedical Engineering Reference
In-Depth Information
This context gives the impression about a design concept of synthetic ECM that
are designed to provide micro-/nano-topographical and mechanical cues to direct
cell migration, proliferation, and differentiation through modulation of actin cyto-
skeleton. Combinatorial controls of these cellular processes are important in tissue-
and organ- development and growth, maintenance, and regeneration. Thus, the
design concept of the synthetic ECM is important to develop functional biomateri-
als as cell- and tissue-culture substrate used
in vitro
and as scaffolds used
in vivo
in
regenerative medicine.
This chapter proposes a design concept of the topographical and mechanical
properties of a synthetic ECM to control cell migration, proliferation and differ-
entiation from biophysical basis to biomedical applications of the designed
ECM. First, in Sect.
11.2
, we explain physiological roles of actin cytoskeleton,
which is a biophysical basis for designing the synthetic ECM. Second, in
Sect.
11.3
, we explain how the actin cytoskeleton is modulated via topographical
and mechanical cues provided by ECM. In Sect.
11.4
, these insights are put
together into a design concept of the topographical and mechanical properties of
the synthetic ECM that gives cues for combinatorial control of cell migration,
proliferation, and differentiation. Furthermore, possible biomedical applications
of the synthetic ECM are presented.
11.2
Physiological Roles of Actin Cytoskeleton
As described throughout this topic, the physiological role of the actin cytoskeleton
is well known as it provides mechanical support and endogenous force generation
for formation of a cell shape and for migration. Furthermore, a number of studies
have demonstrated another signifi cant role of the actin cytoskeleton: it offers
dynamic epigenetic memory for guiding cell fate, in particular, cell proliferation,
apoptosis and stem cell differentiation.
11.2.1
Force Generation for Cell Migration
Cell migration is essential for morphogenetic processes in tissue development,
maintenance, and regeneration. Cell migration involves several basic processes,
including cytoplasmic protrusion at the leading edge and generating force against
the ECM to move the cell body forward as explained in detail in Chaps.
1
and
2
.
Although these basic processes are shared by each type of cell migration, different
cell types exhibit different modes of migration related to their specifi c functions
(Friedl and Wolf
2010
).
Individual cells, with an actin cytoskeleton predominantly in the cortex and
migrating while loosely attached to the ECM, exhibit a rounded shape with amoe-
boid migration (Fig.
11.1a
). In contrast, cells with well-bundled actin stress fi bers—
