Biomedical Engineering Reference
In-Depth Information
the so-called JAKs (Janus kinases). These kinases then operate on the STATs (signal trans-
ducers and activators of transcription) that transmit the signal into the nucleus.
The kinetics of this process are complex, and detailed analyses are becoming available for
the epidermal growth factor and other signal transduction processes.
Direct Cell-Cell Contact: Insoluble Factors 1
Cells are equipped with proteins on their surface called cell adhesion molecules (CAMs).
These include the cadherins (adhesion belts, desmosome) and connexins (gap junctions).
These molecules are involved in direct cell-to-cell contact. Some CAMs are known as the
cell junction molecules, since junctions are formed between the adjacent cells, allowing
for direct cytoplasmic communication. Such junctions are typically on the order of 1.5 nm
in diameter and allow molecules below about 1,000 D to pass between cells.
A growing body of literature is showing how fluid mechanical shear forces influence cell
and tissue function. Tissue function has a significant mechanical dimension. At the cellular
level, the mechanical role of the cytoskeleton is becoming better understood. Signals may
be delivered to the nucleus by cellular stretching in a way that is similar to the method in
which growth factor binding to a receptor delivers signals. The cell-surface integrin recep-
tors thus can perform as “mechanical transducers” of important signals. Further, cells have
specific locations within a tissue, and long-distance information must be transmitted
between cells via weak mechanical interactions. The mechanical characteristics of the
cellular microenvironment are thus of importance, as are the mechanical properties of
the cells themselves. The study of mechanically induced changes in cell function and
mechanotransduction of cell signals is a rapidly growing area with great relevance to
tissue engineering.
Cell-Matrix Interactions: Insoluble Factors 2
The extracellular matrix (ECM) is composed of a complex weave of fibers, struts, and
gels that fills the spaces between cells in a tissue and interconnects the cells and their cyto-
skeletal elements. The ECM is multifunctional and provides tissue with mechanical support
and cells with a substrate on which to migrate, as well as a place to locate signals for
communications. The ECM thus has structural as well as instructional functions. It is
dynamic and is constantly being modified. For instance, ECM components are degraded
by metalloproteases and can be regenerated via cellular production. Many tissues remodel
their matrix to some degree. For example, in cardiac muscle about 3 percent of the matrix is
turned over daily.
The ECM is comprised of a large number of components that have varying structural
and regulatory functions. On the cell surface, there are a number of adhesion and ECM
receptor molecules that facilitate cell-ECM communications. These signals contain instruc-
tions for migration, replication, differentiation, and apoptosis. The nature of these signals
is governed by the composition of the ECM, which in turn can be altered by the cells found
in the tissue. Thus, many cellular fate processes can be directed by the ECM, and it provides
a means for cells to communicate. The signals in the ECM are more stable and can be made
more specific and stronger than those delivered by diffusible growth factors. The compo-
nents of the ECM and their functions are summarized in Table 6.5.
