CHARACTERIZATION OF THE ADHESIVE INTERACTIONS BETWEEN CELLS AND BIOMATERIALS - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 165

has been found not only to be tissue specific but also cellularly specific within a
single tissue, such as in different strata in the same stratified epithelial tissue. 27
Because of this specificity, it is hypothesized that desmosomes may play a role in
epithelial tissue differentiation.
Other subclasses of the cadherin superfamily include the protocadherins, the
7TM-cadherins, the T-cadherins, and the FAT family of cadherins. Protocadherins
are a very large family of cadherins that exhibit moderate adhesive activity. The
major subfamilies of the protocadherins are

-protocadherin and CNR-cadherin.
Although the exact function of these cadherins is still unclear, it is hypothesized that
they play a role in the development of the nervous system. 19 The 7TM-cadherins are
a family of membrane proteins that contain seven transmembrane segments and
function similarly to G protein-coupled receptors and have a large impact on cell
adhesion related signaling. The Flamingo cadherin is one of the better studied 7TM-
cadherins, and it is thought to have an important role in establishing the polarity of
the cell. 19
T-cadherins are the only type of cadherins that have no transmembrane or
cytoplasmic domains. Rather, the T-cadherin is linked to the membrane through
a glycosylphosphatidylinositol (GPI) anchor. GPI-anchored proteins are thought to
be more densely located within lipid raft domains, which are known signaling
platforms. Research in cardiomyocytes suggested that T-cadherins may also be
located in lipid rafts and therefore function in cell signaling. 19,28 Cadherins in the
FAT family have very large extracellular domains and are most highly expressed by
proliferating cells that are undergoing development rather than in adult tissues. This
observation has led to speculation that FAT cadherins have functions that are beyond
cell-cell adhesion and are more closely related to cell migration and maturation
during morphogenesis. 19
Similar to the research that has been done to exploit integrin-ligand interactions
for tissue engineering, the cell-cell interactions and downstream effects that result
from cadherin activation could be of interest in many applications, including stem
cell differentiation studies and engineering of epithelial and endothelial layers.
Biomaterial design should consider the inclusion of cadherin-like particles on the
surface to promote cell attachment and necessary interaction between cells.

m

7.2.3 Immunoglobulins

Immunoglobulins are a superfamily of membrane proteins that share a common
domain referred to as the Ig fold motif. 29 Igs have been found to have an important
role in the activation and regulation of the immune system because immune cells
must be nonadherent when circulating the blood and lymph but become adherent
when migrating through tissue. 30
There are three main subfamilies of Igs, which function similarly in different
tissue types. The intracellular cell adhesion molecule (ICAM) family are type I
transmembrane glycoproteins that contain two to nine Ig domains. ICAM-1 is
expressed constitutively in venular endothelial cells and some leukocytes and can
be stimulated by cytokines. 29 ICAM-1 can serve as a ligand to some integrins, which