132 Chapter 6
Extracellular Matrix
The cells that compose the organs of our body are embedded
within the extracellular material of connective tissues ( fig. 6.1 ).
This material is called the extracellular matrix, and it con-
sists of the protein fibers collagen and elastin (see chapter 2,
fig. 2.30), as well as gel-like ground substance. The interstitial
fluid referred to previously exists primarily in the hydrated gel
of the ground substance.
Although the ground substance seemingly lacks form (is
amorphous) when viewed under a microscope, it is actually a
highly functional, complex organization of molecules chemi-
cally linked to the extracellular protein fibers of collagen and
elastin, as well as to the carbohydrates that cover the outside
surface of the cell’s plasma membrane (see chapter 3, fig. 3.2).
The gel is composed of glycoproteins (proteins with numer-
ous side chains of sugars) and molecules called proteoglycans.
These molecules (formerly called mucopolysaccharides ) are
composed primarily of polysaccharides and have a high con-
tent of bound water molecules.
The collagen and elastin fibers have been likened to the rein-
forcing iron bars in concrete—they provide structural strength to
the connective tissues. One type of collagen (collagen IV; there
are about 15 different types known) contributes to the basal lam-
ina (or basement membrane ) underlying epithelial membranes
(see chapter 1, fig. 1.12). By forming chemical bonds between
the carbohydrates on the outside surface of the plasma membrane
of the epithelial cells, and the glycoproteins and proteoglycans
of the matrix in the connective tissues, the basal lamina helps to
wed the epithelium to its underlying connective tissues ( fig. 6.1 ).
The surface of the cell’s plasma membrane contains gly-
coproteins that affect the interactions between the cell and
its extracellular environment. Integrins are a class of gly-
coproteins that extend from the cytoskeleton within a cell,
through its plasma membrane, and into the extracellular
matrix. By binding to components within the matrix, they
serve as a sort of “glue” (or adhesion molecule) between
cells and the extracellular matrix. Moreover, by physically
joining the intracellular to the extracellular compartments,
they serve to relay signals between these two compartments
(or integrate these two compartments—hence the origin of
the term integrin ).
Through these interactions, integrins help to impart a
polarity to the cell, so that one side is distinguished structurally
and functionally from another (apical side from basal side, for
example). They affect cell adhesion in a tissue and the ability
of certain cells to be motile, and they affect the ability of cells
to proliferate in their tissues. Extracellular matrix proteins and
proteoglycans also bind to secreted regulatory chemicals, par-
ticularly various growth factors, and help to deliver these to
integrins and receptor proteins at the cell surface (receptor pro-
teins are discussed in section 6.5).Categories of Transport
Across the Plasma Membrane
Because the extracellular fluid is either blood plasma or
derived from blood plasma, the term plasma membrane is used
for describing the membrane around cells that separates the
intracellular from the extracellular compartments. Molecules
that move from the blood to the interstitial fluid, or molecules
that move within the interstitial fluid between different cells,
must eventually come into contact with the plasma membrane
surrounding the cells. Some of these molecules may be able
to penetrate the membrane, while others may not. Similarly,
some intracellular molecules can penetrate, or “permeate,” the
plasma membrane and some cannot. The plasma membrane is
thus said to be selectively permeable.
The plasma membrane is generally not permeable to pro-
teins, nucleic acids, and other molecules needed for the struc-
ture and function of the cell. It is, however, permeable to many
other molecules, permitting the two-way traffic of nutrients
and wastes needed to sustain metabolism. The plasma mem-
brane is also selectively permeable to certain ions; this permits
electrochemical currents across the membrane used for pro-
duction of impulses in nerve and muscle cells.
The mechanisms involved in the transport of molecules
and ions through the plasma membrane can be categorized
in different ways. One way is to group the different transport
processes into those that require membrane protein carriers
(described in section 6.3) and those that do not utilize mem-
brane carriers.1. Carrier-mediated transport
a. Facilitated diffusion
b. Active transportCLINICAL APPLICATION
There is an important family of enzymes that can break down
extracellular matrix proteins. These enzymes are called
matrix metalloproteinases (MMPs) because of their need
for a zinc ion cofactor. MMPs are required for tissue remodel-
ing (for example, during embryonic development and wound
healing), and for migration of phagocytic cells and other
white blood cells during the fight against infection. MMPs
are secreted as inactive enzymes and then activated extra-
cellularly; however, they can contribute to disease processes
if they are produced or activated inappropriately. To prevent
this from happening, there are other enzymes (abbreviated
TIMPs ) that inhibit the MMPs.
For example, MMPs are involved in the ability of a
cancerous tumor to metastasize, or invade different loca-
tions. The MMPs are peptidases that break down extracel-
lular matrix proteins and cell adhesion proteins, allowing
the tumor cells to migrate across the basement membrane
and into blood and lymphatic vessels. The destruction of
cartilage protein in arthritis may also involve the action of
these enzymes, and an imbalance between the MMPs and
TIMPs is believed to contribute to cardiovascular and neural
diseases.