Unit 11 - The extracellular matrix

11.1 Matrix structural proteins

11.2 Matrix polysacharides
 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

Different extracellular matrices:

1- Basal laminae extracellular matrices – thin and sheetlike
matrix previously called basement membranes that can be
found under the epithelial cell layers or surrounding muscle
cells, adipose cells, and peripheral nerves.

2- Extracellular matrices of connective tissues – Example: the

loose connective tissue (“tejido conectivo laxo”) under
epithelial cell layers that consists predominantly of an
extracellular matrix in which fibroblasts are distributed

3- Extracellular matrices from specialised connective tissue,

such as bone, tendon, and cartilage. These tissues have a largely
extracellular matrix, which is principally responsible for their
structure and function

The differences between various types of extracellular matrices

result from both quantitative variations in the types or amounts
of their constituents and from modifications in their
organization.
 1. Matrix Structural proteins

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 contains also adhesion proteins that link components
of the matrix both to one another and to attached cells.

1- 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
Gly-X-Y:

Gly - Glycine
X - Proline
Y - Hydroxyproline or hydroxylysine

Glycine- the smallest amino acid, with a side chain consisting only of a 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 stabilize 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
 1. Matrix structural proteins

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 chains 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
nonhelical segment 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 terminusof 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.

Frequently, the fibrils further associate with one another to form

collagen fibers, which can be several micrometers in diameter.
 1. Matrix structural proteins

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 nonhelical 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.
 Glucosamine 2- Matrix polysaccharides 2. Matrix polysaccharides

The matrix structural proteins (Colagens and elastin fibers) are embedded in
gels formed from polysaccharides called glycosaminoglycans (GAGs) which
consist of repeating units of disaccharides

Galactosamine 1- One sugar of the disaccharide is

N-acetylglucosamine:
-Keratan sulfate
-Heparan sulfate
-Hyaluronan
2- One sugar of the disaccharide is
N-acetylgalactosamine:
-Dermatan sulfate
-Condoitrin 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, 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.
 3- Matrix adhesion proteins 3. 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. Matrix adhesion proteins

ECM Protein components - Proteases

3. Metalloproteases
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 of proteases to be identified was an enzyme that digests collagen (the Collagenase enzyme). This
enzyme was the founding member of what become 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