The extracellular matrix
Extracellular matrices consist of a variety of secreted proteins and polysaccharides. Several
of the proteins and polysaccharides found in the extracellular matrix are also found closely
associated with the plasma membrane
Components of the extracellular matrix:
Extracellular matrices are composed of tough fibrous proteins (Structural proteins)
embedded in a gel-like polysaccharide ground substance.
Extracellular matrix also contains adhesion proteins that link components of the matrix both
to one another and to attached cells.
Matrix structural proteins (collagen and elastic fibers)
a) COLLAGEN is the single most abundant protein in animal tissues.
● The collagens are a large family of proteins containing at least 27
different members.
● They are characterized by the formation of triple helices in which
three polypeptide chains are wound tightly around one another in a
rope like structure
The triple helix domains of the collagens consist of repeats of the amino acid
sequence
Glycine- the smallest amino acid, with a side chain consisting only of hydrogen.
It is required in every third position in order for the polypeptide chains to pack together close
enough to form the collagen triple helix
Proline and Hydroxyproline- their ring structure stabilizes the helical conformations of the
polypeptide chains. The hydroxyl groups of these modified amino acids are thought to
stabilize the collagen triple helix by forming hydrogen bonds between polypeptide chains.
These amino acids are rarely found in other proteins
Different types of collagen have different roles in various kinds of extracellular matrices
Collagen type 1
Is the most abundant type of collagen. It forms the collagen fibrils
that are the basic structural components of connective tissues.
The polypeptide chain contains a thousand amino acids or 330
[Gly-X-Y] repeats.
Collagen is secreted by the cells and thereafter, these collagens
assemble into collagen fibrils.
The fibril-forming collagens are synthesized in cells as soluble
precursors (procollagens) that contain non helical segments at both
ends of the polypeptide chain.
Procollagen is cleaved to collagen after its secretion, so the
assembly of collagen into fibrils takes place only outside the cell.
Then, the triple helical molecules are associated in regular
staggered arrays (“matrices escalonadas”).
The molecules overlap and leave a short gap between the
N-terminus of one molecule and the C terminus of the next. The
assembly is further strengthened by the formation of covalent
crosslinks between the side chains of lysine and hydroxylysine
residues, primarily at the ends of the molecules.
Collagen type IV
Is a network-forming collagen found in basal laminae matrices. The Gly-X-Y repeats of these
collagens are frequently interrupted by short non helical sequences. Because of these
interruptions, the network-forming collagens are more flexible than the fibril-forming
collagens. Consequently, they assemble into two- dimensional cross-linked networks instead
of fibrils
Other types of collagen forms anchoring fibrils, which link some basal laminae to underlying
connective tissues. And some collagens are transmembrane proteins that participate in
cell-matrix interactions.
b) ELASTIC FIBERS are structural proteins particularly abundant in organs that regularly
stretch and then return to their original shape.
Lungs stretch each time a breath is inhaled and return to their original shape with each
exhalation.
Elastic fibers are composed of ELASTIN, which is cross-linked into a network by covalent
bonds formed between the side chains of lysine residues (similar to those found in collagen).
This network of cross-linked elastin chains behaves like a rubber band, stretching under
tension and then snapping back when the tension is released.
Matrix polysaccharides
The matrix structural proteins (Collagens and elastin fibers) are
embedded in gels formed from polysaccharides called
glycosaminoglycans (GAGs) which consist of repeating units of
disaccharides
1- One sugar of the disaccharide is N-acetylglucosamine:
-Keratan sulfato -Heparan sulfate -Hyaluronan
2- One sugar of the disaccharide is N-acetylgalactosamine:
-Dermatan sulfate -Chondroitin sulfate
Second sugar: is usually acidic Glucuronic acid or iduronic acid
With the exception of hyaluronan, these sugars are modified by the
addition of sulfate groups. Consequently, GAGs are highly negatively
charged. Like the pectins of plant cell walls, they bind positively
charged ions and trap water molecules to form hydrated gels,
thereby providing mechanical support to the extracellular matrix.
Hyaluronan is also the only GAG that occurs as a single long
polysaccharide chain. Like cellulose, it is synthesized at the plasma
membrane by a transmembrane hyaluronan synthase.
All of the other GAGs are linked to proteins (attached to serine
residues) to form proteoglycans.
Many proteoglycans interact with hyaluronan to form large
complexes in the extracellular matrix.
Matrix adhesion proteins
These proteins are responsible for linking the components of the matrix to one another and
to the surfaces of cells. They interact with collagen and proteoglycans to specify matrix
organization and are the major binding sites for cell surface receptors, such as integrins.
1. Fibronectin, which is the principal adhesion protein of connective tissues.
- It is a dimeric glycoprotein consisting of two polypeptide chains, each
containing nearly 2.500 amino acids.
- It is often crosslinked into fibrils.
- It has binding sites for both collagen and proteoglycans, so it
cross-links these matrix components.
- It has a domain recognized by cell surface receptors (such as integrins)
Thus, it is responsible for the attachment of cells to the extracellular matrix.
2. Laminins Adhesion proteins of the laminin family. They are the principal components and
the major organizers of basal laminae assembly. Laminins: - Are T-shaped heterotrimers of
α, β, and y subunits,
- Can self-assemble into meshlike polymers (like type IV collagen).
- Have binding sites for cell surface receptors such as integrins, and proteoglycans.
- Are tightly associated with another adhesion protein, called Nidogen, which also
binds to type IV collagen.
As a result of these multiple interactions, laminin, nidogen, type IV collagen, and the
proteoglycans form crosslinked networks within basal laminae.
3. Metalloproteases
ECM Protein components - Proteases
Animal cells can modify the extracellular matrix as they grow and migrate. Cells secrete:
1- Several types of enzymes able to digest GAG
2-Proteases –Enzymes able to digest proteins
One of the first proteases to be identified was an enzyme that digests collagen (the
Collagenase enzyme). This enzyme was the founding member of what became the matrix
metalloprotease family which consists of 23 proteases in humans.
These enzymes digest a variety of matrix proteins, including collagen and laminin, as well as
cell surface receptors and adhesion molecules. The metalloproteases play important roles
not only in the normal movements of cells during development but also in the growth and
metastasis of cancers or in natural processes such as angiogenesis.
