154
UNIT ONE
R
ather than being just “f
ller” between cells,
the extracellular matrix (ECM) is a com-
plex and changing mix oF molecules that
modiFies the tissue to suit diFFerent organs and
conditions. Not only does the ECM serve as a scaF-
Folding to organize cells into tissues, but it relays
the biochemical signals that control cell division,
di±
erentiation, repair, and migration.
The ECM has two basic components: the base-
ment membrane that covers epithelial cell surFaces,
and the rest oF the material between cells, called
the interstitial matrix. The basement membrane
is mostly tightly packed collagenous Fibers From
which large, cross-shaped glycoproteins called
laminins extend. The laminins (and other glyco-
proteins such as f
bronectin, the proteoglycans,
and tenascin) traverse the interstitial matrix and
contact receptors, called integrins, on other cells
(Fig. 5A). In this way, the ECM connects cells into
tissues. At least twenty types oF collagen and pre-
cursors oF hormones, enzymes, growth Factors, and
immune system biochemicals (cytokines) comprise
the various versions oF the ECM. The precursor mol-
ecules are activated under certain conditions.
The components oF the ECM are always
changing, as its cells synthesize proteins while
enzymes called proteases break down speciFic
proteins. The balance oF components is impor-
tant to maintaining and repairing organ struc-
ture. Disrupt the balance, and disease can result.
Here are three common examples:
Cancer
The spread oF a cancerous growth takes advan-
tage oF the normal ability oF Fibroblasts to con-
tract as they close a wound, where they are
replaced with normal epithelium. Chemical
signals From cancer cells make f
broblasts more
contractile (myof
broblasts), and they take on the
characteristics oF cancer cells. At the same time,
alterations in laminins loosen the connections oF
the f
broblasts to surrounding cells. This abnor-
mal Flexibility enables the changed Fibroblasts
to migrate, helping the cancer spread. Normally,
f
broblasts secrete abundant collagen.
Liver Fibrosis
In Fibrosis, a part oF all chronic liver diseases,
collagen deposition increases so that the ECM
exceeds its normal 3% oF the organ. Healthy
liver ECM sculpts a Framework that supports the
epithelial and vascular tissues oF the organ. In
response to a damaging agent such as a virus,
alcohol, or a toxic drug, hepatic stellate cells
secrete collagenous f
bers in the areas where the
epithelium and blood vessels meet. Such limited
Fibrosis seals oFF the aFFected area, preventing
its spread. But iF the process continues—iF an
inFection is not treated or the noxious stimulus
not removed—the ECM grows and eventually
blocks the interaction between liver cells and
the bloodstream. The liver tissue hardens, a dan-
gerous condition called
cirrhosis.
Heart Failure and Atherosclerosis
The heart’s ECM organizes cells into a three-
dimensional network that coordinates their con-
5.1
CLINICAL APPLICATION
The Body’s Glue: The Extracellular Matrix
tractions into the rhythmic heartbeat necessary
to pump blood. This ECM consists oF collagen,
f
bronectin, laminin, and elastin surrounding car-
diac muscle cells and myof
broblasts and is also in
the walls oF arteries. Heart Failure and atherosclero-
sis re²
ect imbalances oF collagen production and
degradation. As in the liver, the natural response oF
ECM buildup is to wall o±
an area where circulation
is blocked, but iF it continues, the extra sca±
olding
sti±
ens the heart, which can lead to heart Failure.
In atherosclerosis, excess ECM accumulates on the
interior linings oF arteries, blocking blood Flow.
During a myocardial inFarction (heart attack), colla-
gen synthesis and deposition increase in a±
ected
and nona±
ected heart parts, which is why damage
can continue even aFter pain starts. ³rom Science
To Technology 5.2 (p. 166) and From Science to
Technology 15.1 (p. 566) discuss engineering a
semisynthetic replacement heart.
FIGURE 5A
The extracellular matrix (ECM) is a complex and dynamic meshwork oF various
proteins and glycoproteins. Collagen is abundant. Other common components include integrins
that anchor the ECM to cells, proteoglycans, and f
bronectin. The ECM may also include precursors
oF growth Factors, hormones, enzymes, and cytokines. It is vital to maintaining the specialized
characteristics oF tissues and organs.
Actin filament
Proteoglycan
Fibronectin
Collagen
fiber
Integrin
Cell Membrane
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