Specific Adhesion of Soft Elastic Materials - Structural Interfaces and Attachments in Biology - page 147

critical role in cell migration, spreading, differentiation, growth, motility, apoptosis,
and tissue formation [ 1 ]. Cells adhere to substrates through the formation of focal
complexes (FXs), focal adhesions (FAs), and related ECM adhesions. The FXs
are small, dot-like, clusters of ligand-receptor bonds that can further develop into
FAs, which are micron-sized, complex multi-molecular assemblies linked on one
side to the ECM via membrane-bound receptors and on the other side to actin
stress fibers in the cytoskeleton. FAs can be dissociated when strong mechanical
forces are applied. Importantly, recent experiments also show that cells use
mechanical force as a signal to strengthen initial integrin-ECM adhesions into
FXs [ 2 ]. The FXs are usually continuously formed and turned over under the
protruding lamellipodia [ 3 ], which may or may not further develop into mature
FAs. The size, assembly, and stability of FAs depend on the mechanical forces
appliedtothem[ 4 - 6 ], as well as to the mechanical properties of the ECM [ 7 , 8 ]
and actin cytoskeleton [ 9 ]. A typical cell will attach and apply traction forces to
the ECM [ 10 ] via myosin II motor proteins on the actin filament system that link
directly to adhesion sites. Inhibition of myosin II leads to accumulation of
immature FXs and to the disappearance of mature FAs [ 6 , 11 - 14 ], while activa-
tion of myosin II induces FA assembly [ 15 - 17 ]. On the other hand, application of
external forces to FAs is found to stimulatetheirgrowthinthedirectionofthe
force even when myosin II activity is suppressed [ 18 ]. Therefore, irrespective of
their origin, mechanical forces seem to play a key role in the growth and stability
of FAs.
The size of mature FAs on hard substrates can reversibly increase or decrease in
response to the applied force, with stress maintained near a constant value of ~5.5 kPa
independent of cell type [ 19 ] but dependent upon matrix stiffness. Force affects FA
dynamics most strongly when the substrate is sufficiently stiff; large FAs cannot be
formed on very soft substrates [ 7 , 20 , 21 ]. Traction forces transmitted through focal
adhesions generate significant substrate displacements when the substrate is com-
pliant, and various gel systems have emerged that allow not only quantitative study
of the tractions but also reveal wide-ranging and surprising biological effects of
matrix elasticity, not only on motility and proliferation, but even on stem cell
differentiation [ 22 ].
Details about these mechanical, chemical, and biological interactions in single
cells and biomolecules remain elusive [ 23 ]. Despite many fascinating studies on
cell adhesion, there is still no theoretical framework to understand the different
experimental observations and complex interplay between the physical properties
of the cell's environment, including the role of matrix properties, in directing the
cell's behavior. Consequently, our understanding of the mechanics of cell adhe-
sion is still quite fragmented in terms of theoretical models. It will be challenging
to develop theoretical models that explain experimental observations about the
effects of cellular contractile or applied forces, substrate stiffness, and adhesion
size on the stability and growth/shrinkage of FAs as well as other adhesion
assemblies.