The Cell–Surface Interaction - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 19

3.4 Mechanotransduction
Focal contacts are protein complexes that constitute the primary attachment which
is essential for long-term adhesion. Apart from integrins, focal adhesions consist of
specific proteins such as talin, a-actinin and vinculin filaments that interact with
the cytoskeleton on the cytoplasmic side. Through focal adhesions, cells react to
extrinsic chemical and mechanical signals from the cell-cell contact or cell-ECM
components. Signal propagation is achieved via direct and indirect mechano-
transduction, both of which are explored here in basic terms. The reader will be
directed to more in-depth sources throughout.
3.4.1 Direct Mechanotransduction
Direct mechanotransduction utilizes conformational changes in focal adhesions
and cytoskeletal conformation to pass information about the ECM topography to
the nucleus as mechanical signals [ 89 ]. The phenomenon of how the cell relays
mechanical signals from the environment may be explained by two theories—
cellular tensegrity [ 90 ] and percolation [ 91 ]. The theory of cellular tensegrity
(tensional integrity) of Ingber [ 90 , 92 ] was adapted from civil engineering prin-
ciples that define tensegrity systems that stabilize their shape by continuous ten-
sion and not by continuous compression. According to Ingber's theory, a cell is a
prestressed tensegrity structure where microtubules act as load bearers and
microfilaments are under tension. In addition, intermediate filaments serve as a
tensile mode that interconnects and stiffens the entire cytoskeleton and nuclear
lattice through tension. The tensional prestress, generated by actomyosin inter-
actions in cortical and contractile stress fibres anchored to the focal adhesions, is a
major determinant of cell and nuclear stability [ 90 ]. This model assumes that
mechanical signals can be transferred across the cell membrane by ECM receptors
and transduced into a chemical response at the site of the bound receptor.
The theory of percolation of Forgacs [ 91 ] involves an interconnected network
system composed of cytoskeleton units, akin to a spider's web, for transducing
mechanical signals. This network spans the distance from the membrane to the
nucleus, where it connects with the nucleus laminin. The physical properties of
cytoplasm determine the speed, whereas the interconnected network allows
redundancy, which means the signal can arrive through several channels. This
model provides speed and redundancy in signal transduction from the membrane
to the nucleus. Fundamentally, in this model a threshold of components is required
for a critical concentration to be reached and if this threshold is achieved, prop-
agation of the signal via the cytoskeleton to the nucleus will be accomplished.
Several fundamental differences exist between the theories. Firstly, tensegrity
does not allow for functional redundancy, which is required for reliable signalling
to be achieved. Secondly, tensegrity structures adhere to strict rules of stability,
i.e. they contain the absolute minimum of structural components required for