Biomedical Engineering Reference
In-Depth Information
engineering, elucidation of the ECM structure and biology also has a rather critical
implication. Dynamic interactions between ECM and cell must be characterized
and understood at the molecular level for desired manipulation of the ECM that
lead to successful tissue-engineering applications. Congruent with the current
research emphasis on nanotechnology, tissue-engineering methodologies will
likely be refi ned and improved by replication of the complex features of natural
ECM at the micro- and nanoscale.
Composition and Architecture of ECM
Major ECM Molecules
The composition of the ECM may be classifi ed into at least fi ve major categories
of components. Molecules found in the ECM include (1) structural proteins, such
as collagen and elastin; (2) adhesion proteins, such as fi bronectin and laminin; (3)
soluble growth factors and cytokines; (4) proteoglycans; and (5) tissue-specifi c
molecules. First, collagen, with at least known 21 subtypes in its family, is the
major protein that comprises the ECM. Each type-I collagen molecule, for
instance, contains three chains (called a chains) twisted around each other to form
a triple helix, and lateral interactions of triple helices of collagens result in the
formation of fi brils roughly 10-300 nm diameter and up to hundreds of micron
length in mature tissues (Alberts et al. 2002 ). The triple helix gives the collagen a
rigid structure that maintains the mechanical and structural integrity of tissues.
There exist several different a chains that are found in various combinations in
the collagen subtypes. Second, fi bronectin, the next largest quantity of proteins
found in the ECM, is one of the glycoproteins involved in cell adhesion to the
ECM and cell migration. It exists as a dimer composed of two very large subunits
joined by a pair of disulfi de bonds near the carboxyl termini (Alberts et al. 2002 ) .
Each subunit is folded into a series of functionally distinct domains separated by
regions of fl exible polypeptide chains 60-70-nm long and 2-3-nm thick. Third,
growth factors and cytokines are the examples of signaling proteins solubilized in
the ECM that can stimulate cells to grow, migrate, and mediate cell-cell commu-
nications (Perris and Perissinotto 2000 ; Brownlee 2002 ; Kleinman et al. 2003 ) .
These generally small signaling molecules can infl uence the cell by binding to a
receptor expressed on the cell surface and activate the receptor-mediated signaling
transduction cascades. Fourth, macromolecules found in the ECM include proteo-
glycans and glycosaminoglycan (GAG). Proteoglycans consist of one or more GAG
chains attached to a core protein. Unlike glycoproteins with one or more oligosac-
charide chains covalently bound to amino acid side chains, proteoglycans contain
much more carbohydrate by weight, mostly in the form of long, unbranched, GAG
chains rather than short, branched, oligosaccharide chains found in glycoproteins
(Alberts et al. 2002 ). Proteoglycans are thought to play a key role in chemical
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