Mechanical Stretching and Signaling Pathways in Adipogenesis - The Mechanobiology of Obesity and Related Diseases - page 39

Since ASCs indeed consist of a heterogeneous MSC population, one must purify or
enrich cells possessing the desired differentiation capabilities.
While conventional methods, such as flow cytometry, have been less efficient in
purifying or enriching cells, Darling and colleagues have demonstrated that atomic
force microscopy can discriminate cellular mechanical properties by testing
individual cells, which would be a predictive biomarker of ASCs clonal differ-
entiation capability [ 52 , 53 ]. Undifferentiated ASCs appear larger in cell-size, are
less viscous, and this elastically compliant ''softer'' population has been shown to
be more adipogenic, whereas a smaller, more viscous, and less compliant ''stiffer''
population would exhibit more osteogenic and chondrogenic potentials, respec-
tively [ 53 , 54 ]. Intrinsic cellular resistance against deformation (elasticity) and
flow (viscosity) would affect the cellular mechanical properties [ 54 ]. In this regard,
matrix elasticity and stiffness, which is controlled by variable compliant poly-
acrylamide gel, appear to overcome the effects of soluble induction factors, and
show significant influence to specify the differentiation lineage and commitment of
MSCs [ 55 ]. This mechanism is inhibited almost completely by the blebbistatin, an
inhibitor of non-muscle myosin II ATPase, suggesting the involvement of a
cytoskeletal control in the determination of mesenchymal stem cell fates, including
adipogenesis, osteogenesis, and myogenesis.
Cristancho and colleagues have demonstrated the molecular basis of the
repression of cell structure related genes that are involved in the cytoskeletal
control during adipocyte differentiation [ 56 ]. The actin cytoskeleton is responsible
for morphology of cells and considered to be the primary contributor to cellular
mechanical properties [ 54 ].
Furthermore, mechanical forces, including cell stretching, evokes remodeling
of the actin cytoskeleton (Fig. 3 ) which interacts with several cellular signals, such
as Rho-GTPase signaling (see Sect. 3.4 ) and very recently found G-actin release
[ 50 , 57 ].
3.3 Extracellular Matrix-Integrin Interaction
Adipocyte differentiation is associated with a dramatic alteration in cell mor-
phology. Adipogenic differentiation of mesenchymal stem cells and/or preadipo-
cytes is accompanied by the changes in cell-shape from fibroblastic to spherical/
rounded and finally to hypertrophied morphologies through extensive cytoskeletal
reorganization. It is well documented that extracellular matrix (ECM) is not only a
scaffold for the cell to maintain tissue/organ construction, but also regulates many
cellular functions, including cell-shape, survival, proliferation, migration, and
differentiation [ 58 ]. ECM has a significant impact on adipocyte differentiation
[ 59 ], presumably through interaction with cell-surface receptors, such as integrins
[ 60 ] and other laminin receptors [ 61 ], or non-integrin collagen receptors (discoidin
domain receptors) [ 62 ].