Extracellular matrix

A.A. Deshmukh
SUK

Ref- The cell: a molecular Approach G.M. Cooper

 1. The extracellular portions of plasma membrane proteins are
generally glycosylated.
2. The carbohydrate portions of glycolipids are exposed on the outer
face of the plasma membrane.
3. Consequently, the surface of the cell is covered by a carbohydrate
coat known as the glycocalyx, which is formed by the oligosaccharides
of glycolipids and transmembrane glycoproteins

An electron micrograph of intestinal epithelium

Glycoprotein
illustrating the glycocalyx (arrows).
Carbohydrate

Glycolipid
Functions: EXTRACELLULAR
SIDE OF
1. Protection to the cell surface MEMBRANE

2. Marker for varieties of Cell-cell interactions

Microfilaments
of cytoskeleton Cholesterol Peripheral IntegralCYTOPLASMIC SIDE
protein
proteinOF MEMBRANE
Figure 7.7
Extracellular matrix that fills the spaces
between cells and binds cells and tissues
together.
consist of a variety of secreted proteins and
polysaccharides.

Figure:
Examples of extracellular matrix Sheets of epithelial cells rest on a
thin layer of extracellular matrix called a basal lamina. Beneath the
basal lamina is loose connective tissue, which consists largely of
extracellular matrix secreted by fibroblasts. The extracellular matrix
contains fibrous structural proteins embedded in a gel-like
polysaccharide ground substance.
Extracellular matrices are composed of tough fibrous proteins embedded in a gel-like
polysaccharide ground

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

The differences between various types of extracellular matrices result from both 1) amounts
of these different constituents and 2) modifications in their organization.
For example,
i. tendons contain a high proportion of fibrous proteins,
ii. cartilage contains a high concentration of polysaccharides that form a firm compression-
resistant gel.
iii. In bone, the extracellular matrix is hardened by deposition of calcium phosphate
crystals.
iv. The sheet like structure of basal laminae results from a matrix composition that differs
from that found in connective tissues.
i. The major structural protein of the extracellular matrix is
collagen, which is the single most abundant protein in animal
tissues.
ii. Large family of proteins containing 27 different members.
iii. Glycine-X-Y, where X is frequently proline and Y is hydroxy
proline
iv. Glycine is required in every third position in order for the
polypeptide chains to pack together close enough to form the
collagen triple helix.
v. because of their ring structure these amino acids stabilize the
helical conformations of the polypeptide chains.
 Type I Collagen:
i. Most abundant type present in connective tissue
ii. Composed of approximately 1000 amino acids or 330 Gly-X-Y repeats

Fibril forming collagens are synthesized

as soluble precursors (procollagens)
that contain nonhelical 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.

(A) Collagen molecule assembles in a regular (A) staggered

array to form fibrils. The molecules overlap by one-fourth of (B) Electron micrograph of collagen fibrils. The
their length, and there is a short gap between the N terminus staggered arrangement of collagen molecules and the
of one molecule and the C terminus of the next. The assembly gaps between them are responsible for the
is strengthened by covalent cross-links between side chains of characteristic cross-striations in the fibrils.
lysine or hydroxylysine residues, primarily at the ends of the
molecules.
i. The association of collagen molecules in fibrils is further strengthened by the formation of covalent crosslinks
between the side chains of lysine and hydroxylysine residues.
ii. Frequently, the fibrils further associate with one another to form collagen fibers, which can be several micrometers in
diameter.
iii. In addition to the fibril-forming collagens, connective tissues contain:
a. fibril-associated collagens, which bind to the surface of collagen fibrils and link them both to one another and to other
matrix components.
b. Basal laminae form from a different type of collagen (type IV collagen), which is a network-forming collagen 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.

c. Another type of collagen forms anchoring fibrils, which link some basal laminae to underlying connective tissues.
d. Other types of collagen are transmembrane proteins that participate in cell-matrix interactions.
• Elastin: Connective tissues also contain elastic fibers, which are particularly abundant in organs
that regularly stretch and then return to their original shape. E.g. The lungs,
• Elastic fibers are composed principally of a protein called 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 fibrous structural proteins of the extracellular matrix are embedded in gels formed from polysaccharides called
glycosaminoglycans (GAGs), which consist of repeating units of disaccharides.
• One sugar of the disaccharide is either N-acetylglucosamine or N-acetylgalactosamine and the second is usually acidic
(either glucuronic acid or iduronic acid).
• These sugars are modified by the addition of sulfate groups(With the exception of hyaluronan ). Consequently, GAGs are
highly negatively charged.
• They bind positively charged ions and trap water molecules to form hydrated gels, thereby providing mechanical support to
the extracellular matrix.

The common sulfated GAGs

• Hyaluronan is the only GAG that occurs as a single long polysaccharide
chain.
• It is synthesized at the plasma membrane by a transmembrane hyaluronan
synthase.
• All of the other GAGs are linked to proteins to form proteoglycans, which
can consist of up to 95% polysaccharide by weight.
• Proteoglycans contain 1 to more than 100 GAG chains attached to serine
residues of a core protein.
• A variety of core proteins (ranging from 10 to >500 kd) have been
identified, a diverse group of macromolecules.
• In addition to being components of the extracellular matrix, some
proteoglycans (syndecans and glypicans) are cell surface proteins that
function along with integrins in cell-cell and cell-matrix adhesion.
 • A number of proteoglycans interact with hyaluronan to form large complexes in the extracellular matrix. A well-
characterized example is aggrecan, the major proteoglycan of cartilage.
• More than a hundred chains of chondroitin sulfate are attached to a core protein of about 250 kd, forming a
proteoglycan of about 3000 kd.
• Multiple aggrecan molecules then associate with chains of hyaluronan forming large aggregates (> 100,000 kd)
that become trapped in the collagen network.

• Proteoglycans also interact with both collagen and other

matrix proteins to form gel-like networks in which the
fibrous structural proteins of the extracellular matrix are
embedded
Matrix Adhesion Proteins:
1. Responsible for Linking the components of the matrix to one another and to the surfaces of cells.
2. They interact with collagen and proteoglycans to specify matrix organization and are the major
binding sites for integrins.
3. Fibronectin is the principal adhesion protein of connective tissues.
a. dimeric glycoprotein consisting of two polypeptide chains, each containing nearly 2500 amino
acids
b. Within the extracellular matrix, fibronectin is crosslinked into fibrils. Fibronectin has binding sites
for a. collagen and b. GAGs
c. A distinct site on the fibronectin molecule is recognized by cell surface receptors (such as
integrins) and is thus responsible for the attachment of cells to the extracellular matrix.
d. Fibronectin proteins vary greatly from tissue to tissue but all are derived by alternative splicing of
the mRNA of a single gene.
Basal laminae contain distinct adhesion proteins of the laminin family

1. Like type IV collagen, laminins can self-assemble into meshlike

polymers.
2. laminin networks are the major structural components of the
basal laminae synthesized in very early embryos, which do
not contain collagen.
3. The laminins also have binding sites for cell surface receptors
such as integrins, type IV collagen, and the heparan sulfate
proteoglycan, perlecan.
4. In addition, laminins are tightly associated with another
adhesion protein, called entactin, which also binds to type IV
collagen. As a result of these multiple interactions, laminin,
entactin, type IV collagen, and perlecan form crosslinked
networks in the basal lamina.
Integrin:
1. The major cell surface receptors responsible for the attachment of
cells to the extracellular matrix
2. Transmembrane proteins consisting of two subunits, α and β
3. More than 24 different integrins formed from combinations of 18
known α subunits and 8 known β subunits.
4. Bind to short amino acid sequences present in multiple
components of the extracellular matrix, including collagen,
fibronectin, and laminin. E.g. binds to Arg-Gly-Asp in fibronectin
5. the integrins serve as anchors for the cytoskeleton.
6. The resulting linkage of the cytoskeleton to the extracellular matrix
is responsible for the stability of cell-matrix junctions.
7. Distinct interactions between integrins and the cytoskeleton are
found at two types of cell-matrix junctions: focal adhesions and
hemidesmosomes.
a. Focal adhesions:
1. attach a variety of cells to the extracellular matrix.
2. the cytoplasmic domains of the β subunits of integrins
anchor the actin cytoskeleton by associating with bundles
of actin filaments through actin-binding proteins such as α
actinin, talin, and vinculin.
b. Hemidesmosomes:
1. Mediate attachment of epithelial cells to basal lamina.
2. At the integrin designated as α6β4, through plectin and
BP230 with intermediate filaments instead of with actin.
3. Bind to long cytoplasmic tail of β4 subunit .
4. BP180 is important in hemidesmosome assembly and
stability. Sequence homology with the transmembrane
collagens.
5. Plectin and BP230 are members of the plakin family, which
is a family of proteins involved in forming links to
intermediate filaments at both hemidesmosomes and
desmosomes.