Biomedical Engineering Reference
In-Depth Information
The Extracellular Matrix
The
extracellular matrix
(ECM) is the material that underlies or surrounds cells in
tissues. The ECM is diverse and abundant in most tissues and comprises up to half the
proteins in the body. Indeed, the collagen family of ECM proteins contains over 25 mem-
bers and accounts for 2 to 30 percent of the proteins in the body. For many years, the
ECM was thought to play an entirely mechanical role binding together cells in specific
arrays. Over the last 30 years, we have learned that the ECM is a major regulator of cell
and tissue function. In addition to mechanical structure, it provides direct biochemical
signals to cells in tissues and also acts as a regulator of many of the soluble growth factors
in tissues.
In epithelial cells the ECM between homotypic cells can be referred to as the “lateral”
ECM, while the proteins underlying the cells (and separating them from underlying
mesenchymal cells) are often referred to as the basal matrix or “basement membrane.”
Two of the primary components of the lateral extracellular matrix are: cell adhesion
molecules, or “CAMs,” which are age- and tissue-specific, and proteoglycans, molecules
containing a protein core to which polymers of sulfated (negatively charged) sugars called
glycosaminoglycans (e.g., heparan sulfates, heparins, chrondroitin sulfates, or dermatan
sulfates) are attached. The basal extracellular matrix consists of basal adhesion molecules
(e.g., laminins or fibronectins) that bind the cells via matrix receptors (integrins) to one
or more types of collagen scaffoldings
.
Thecollagensofonecelllayerarecross-linked
to those of the adjacent cell layer to provide stable coupling between the layers of cells.
In addition, proteoglycans are bound to the basal adhesion molecules, to the collagens,
and/or to the basal cell surface.
The lateral and basal extracellular matrix components of epithelial tissues provide direct
signaling to cells in the form of chronic or persistent signaling. Indirectly, the components
also facilitate signaling by stabilizing cells in appropriate configurations of ion channels,
receptors, antigens, and so on; by influencing intracellular pathways; and by inducing
appropriate cell shapes (flattened or three-dimensional). These interactions enable the cells
to respond rapidly to soluble signals that may derive from local or distant sources. The
soluble factors act by binding to high-affinity molecules called receptors, which can be on
the cell surface or present in the interior of the cell. When the signal binds to its receptor,
a signal initiation response is triggered.
Cell Numbers In Vivo and Orders of Magnitude
The cell densities in human tissues are on the order of 1 billion to 3 billion cells/ml. The
volume of a 70 kg human is about 70,000 ml. Therefore, the human body consists of about
100 trillion (trillion
10
12
) cells. The volume of a “typical” organ is around 100 to 500 ml,
and therefore a typical organ contains about 100 to 1,500 billion (10
9
) cells. Organs are
comprised of
functional subunits
. Their typical linear dimensions are approximately 100
¼
m
m.
The cell number in a cube that is 100
m on each side is estimated to be about 500 to 1,000.
These cell numbers are summarized in Table 6.2.
Based on these estimations, a typical organ will have a few hundred million functional
subunits, each of which is quite small. This number is dictated by the capability of each
subunit and the overall physiological need for its particular function. For example, the
m
