Computational Modeling of Tissue Engineering Scaffolds as Delivery Devices for Mechanical and Mechanically Modulated Signals - Computational Modeling in Tissue Engineering - page 128

Fig. 5 Characteristic magnitudes and time domains of mechanical signals applied in studies of
multipotent cell differentiation. Red data points dilatational stress and black data points deviatoric,
i.e., shear stress. -r indicates hydrostatic compression and +r indicates tension depicted on a log 10
scale in Pa. Yellow region shows dilatational and deviatoric stress ranges predicted to prevail during
cell fate determination in utero. Adapted from [ 2 , 41 ], used with permission
4 Stem Cell Morphology within Mechanical Environments
Stem cell shape has been shown to modulate fate or lineage commitment. Whereas
flattened and spread shape directs stem cells toward osteogenesis, round and
unspread shape directs stem cells toward adipogenesis. The RhoA-ROCK path-
way, involving cytoskeletal remodeling of actin, has been shown to bridge stem
cell shape changes to cell fate commitment [ 32 ].
The cytoskeleton is the main subcellular, mechanical support structure of the
cell. Actin filaments and microtubules play a crucial role in the cellular response to
external forces under fluid flow (Fig. 7 ). Recent studies show interesting rela-
tionships between stem cell shape and fate and the emergence of anisotropy in
stem cells exposed to controlled dilatational and deviatoric stress environments. In
these studies, larger cells at low cell density exhibit a more extensive cytoskeleton,
as measured by amount of tubulin and actin expressed; in contrast, smaller cells at
high cell density exhibit a less extensive cytoskeleton. Furthermore, expression of
tubulin is more significantly affected by shear flow than expression of actin; this is
particularly interesting, given tubulin's role in bearing compressive forces in the
cell compared to actin, which withstands more tensile forces [ 12 ].
The role of nucleus shape change in fate determination is just beginning to be
elucidated. A recent study demonstrated a significant relationship between nucleus
shape and cell seeding protocol; namely, seeding at increasing target density
changes the volume of the cell while changing the shape of the nucleus. Fur-
thermore, changes in nucleus shape are significantly correlated to (fold) changes in