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Cell and Molec
Extracellular Matrix
Extracellular Matrix
• An interconnected network of
macromolecules secreted by the cells
• In most tissues, fibroblast cells are
primarily responsible for secreting the
extracellular matrix
Examples E.M.
• Bone: Most of bone is a rigid extracellular
matrix with only a few cells scattered
through it
• Cartilage: Almost entirely matrix material
• Most glands and blood vessels are
surrounded by a gelatinous extracellular
matrix which has many cells in it
E.M. provides shape and Support,
but also affects:
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Cell shape
Cell motility
Growth
Division
Development of specialized cellular
characteristics
3 Classes of E.M. Molecules
• 1) Glycosaminoglycans & Proteoglycans:
gelatinous substance
• 2) Structural proteins, (collagens, elastin):
give strength and flexibility to the matrix
• 3) Adhesive proteins, (fibronectin, laminin):
promote attachment of cells to the matrix
Ground Substance of E.M.
• Glycosaminoglycans and Proteoglycans
• Glycosaminoglycans are polysaccharides
• They contain repeating disaccharide
containing an amino sugar and at least one
negatively charged sulfate or carboxyl group
• Since they are hydrophilic (sugar) and (-)
charged, they attract H20 and (+) charged
molecules, producing a hydrated gelatinous
material called the ground substance of the
extracellular matrix
Glycosaminoglycans
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Chondroitin sulfate
Keretin sulfate
Heparin
Heparin sulfate
Hyaluronate (hyaluronic acid)
Dermatin sulfate
Proteoglycans
• Most glycosaminoglycans exist attached to
a protein
• A proteoglycan is composed of one core
protein with multiple attached
glycosaminoglycans (may be 95%
polysaccharide)
Cartilage, a proteoglycan matrix
• Cartilage tissue is composed of dozens of
proteoglycan molecules attached to one
long hyaluronate backbone
• This give cartilage its strength and
flexibility properties
Hyaluronic Acid
• H.A. is unusual in that it also exists as a free
polysaccharide
• H.A. is found in high levels in tissues where cells
are moving or actively dividing
• It is found in the surface of cells which are
migrating, but is removed when cells cease to
migrate
• It is thought to be involved in the movement /
migration of cells, possibly by attracting a H2O layer
• H.A. also is seen as a “lubricant” in joints between
bones
Collagen
• Collagen is a group of related proteins (14
types or more).
• 30% of the total protein of a vertebrate is
collagen
• Made of 3 intertwined polypeptide chains:
these alpha chains form a triple helix
Collagen
• 25% of the amino acids in collagen are
glycine
• Another 25% are unusual amino acids
hydroxy proline and hydroxy lysine
• Hydrogen bonding between the OH of the
hydroxy proline and the H of glycine gives
strength to the triple helix
Collagen
• Scurvy, caused by a lack of Vitamin C, is
due to a loss of activity of the enzyme
which produces hydroxy proline.
Therefore, the triple helix is destabilized,
resulting in a loss of structure in the
connective tissue. Bruising, bleeding, and
other connective tissue problems result.
Collagen
• More than 14 types of collagen are formed
by various combination of chains from at
least 20 different genes.
• They exist in one of two forms: banded
fibrils or unbanded filamentous networks
• Larger fibers of collagen form in some
tissues, giving strength to tendons,
cartilage, etc.
Formation of Collagen
• Collagen protein is produced as a precurser chain
with extra amino acids at both ends
• These extra amino acids are necessary for the triple
helix to form
• 3 chains form a triple helix procallogen in the ER
lumen
• The extra A.A.s then prevent the formation of fibrils
• The procallogen is secreted from the cell, the extra
amino acids are removed (by procallogen
peptidases)
• The collagen then spontaneously forms fibrils
• Crosslinks between lysines and hydroxylysines add
strength to the networks/
Other ECM Components
• 1)Elastin: Flexibility, glycine and proline rich
• 2)Fibronectin: one gene, many forms due
to alternative splicing of the RNA
• Attach the cell surface to the ECM.
• Guide cells during migration (embryonic
development, immune response to wounds,
etc.)
• Different domains interact with different
proteins
Other ECM Components
• 3) Laminin: in the basal lamina, a thin sheet of
ECM separating epithalial cells from the
underlying supporting tissues
• Surround many nerve, muscle, and fat cells
• Provides separation of cell types, influences
growth patterns, differentiation, motility
• 4) Integrin receptors: transmembrane proteins
which bind ECM on the outside of the cell, bind
the cytoskeleton on the inside. “Integrate the
organization of the cytoskeleton with that of the
extracellular matrix”
Glycocalyx
• A carbohydrate-rich zone located at the
periphery of many animal cells
• Involved in cell recognition, adhesion, protection
of cell surface, permeability barriers
• “attached glycocalyx”: glycoprotein and
glycolipid carbohydrates
• “unattached glycocalyx”: secreted glycoproteins
and proteoglycans (Extracellular matrix)
Cell Recognition and Adhesion
• Cells seem able to recognize similar cells
and adhere specifically to like cells.
• Early experiment with two color sponges:
cells dis-associated and allowed to reform:
only like cells clumped together
Adhesion Molecules
• N-CAM: neural cell adhesion molecule: involved
in “linking” of neural cells in development
• Appears that N-cam molecules the cell surface
interact with N-cams on the next cell
• Cadherins: A class of Calcium requiring cell
adhesion molecules
• Epithelial, Nervous, Placental (E-cadherin, Ncadherin, P-cadherin): specific interaction with
the same type of cadherin: nerve cells only bind
to nerve cells and so forth.
Carbohydrates and Recognition
and Adhesion
• Most surface recognition and adherin
proteins are glycosylated: it seems that the
carbohydrate is important for the
recognition and adhesion
• Lectins are secreted proteins which can
bind (multiple) carbohydrates: presumed
to be involved in the adhesion process.
Sialic Acid and Cell Aging
• RBCs are removed from circulation by the
spleen after about 3-4 months
• Glycophorin has the carbohydrate sialic
acid at the ends of many carbohydrate
chains
• Loss of sialic acid from the glycoprotein
seems to be part of the way the spleen
recognizes “old” cells to be removed
Cell Junctions
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Three major types of cellular junctions:
1) Tight Junctions
2) Adhesive (Plaque-bearing) junctions
3) Gap junctions
Tight Junctions
• Form permeability barriers across cell
layers (such as the lining of the digestive
tract)
• Also form polarity in cells: prevent diffusion
of proteins within the membrane across
the junction
Plaque-Bearing Junctions
• Provide connections to the cytoskeleton
between two adjacent cells
• Desmosomes: attach to intermediate
filaments: plakoglobin and desmoplakin in
plaque
• Adherins Junctions: provide attachments
to actin filaments: vinculin,( talin in focal
adhesions)
Gap Junctions
• Gap junctions allow passage of small
molecules between adjacent cells
• Are dependent on Ca+ concentration
(close with higher Ca+)
• Made of protein called connexons
Plant Cell Wall
• Plant cells are surrounded by a rigid cell
wall.
• The cell wall, like the extracellular matrix
of animal cells, is formed from material
secreted by the cell.
• Water, gases, ions, and small water
soluble molecules such as sugars and
amino acids can readily diffuse through
the cell wall.
Components of the Cell Wall
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Cellulose
Hemicelluloses
Pectins
Extensins
Lignins
Cellulose
• The most abundant organic macromolecule
on earth.
• Unbranched polymer of glucose units linked
by beta1,4 linkages.
• 50-60 molecules form microfibrils, stabilized
by hydrogen bonds between molecules.
• Microfibrils are often twisted into ropelike
macrofibrils.
• Cellulose macrofibrils are as strong as a
similar sized piece of steel.
Hemicelluloses
• A varied group of polysaccharides.
• Each is a long chain of a single type of sugar
(glucose or xylose) with short side chains.
• The side chains contain several types of sugars:
– Hexoses; glucose, galactose, mannose
– Pentoses; xylose and arabinose
• Hemicelluloses form a coating over the cellulose
helping to bond the cellulose fibrils into a rigid
network.
Pectins
• Pectins are polysaccharides with a backbone of
negatively charged galacturonic acid and rhamnose.
• Pectin side chains are similar to hemicellulose side
chains.
• Proteins crosslink the pectin backbone to the
hemicelluloses.
• Pectin forms a matrix in which the cellulose
microfibrils are embedded, and bind adjacent cell
walls together.
• Pectins trap water, forming a gel like substance which
can vary from fluid to rigid, depending on the
chemical composition of the pectin: pectin is the
gelling agent in jam and jelly.
Extensins
• Extensins are glycoproteins: the peptide
backbone is rich in serine, hydroxyproline,
and lysine.
• Lysine is + charged, and causes extensins to
bind to the – charged pectins.
• Extensins are deposited as a soluble
molecule, but become covalently crosslinked
to one another and to cellulose, forming a
reinforced protein-polysaccharide network.
Lignins
• Lignins are insoluble polymers of aromatic
alcohols found mainly in woody tissues.
• The alcohols are deposited in the cell wall, then
covalently crosslinked by the enzyme
peroxidase.
• This network of lignin accounts for up to 25% of
the dry weight of wood, and gives wood much of
its strength.
• Lignin is second only to cellulose in abundance
in the organic realm.
Cell Wall Synthesis
• Cell wall components are secreted from
the cell.
• The layer of the cell wall farthest from the
cell is secreted first.
• The middle lamella is secreted first.
• The primary cell wall is secreted second,
while the cells are growing.
• The secondary cell wall is secreted by
some cells after they have ceased growth.
Middle Lamella
• Shared by adjacent cells
• Holds the cells togeher.
Primary Cell Wall
• 100-200 nm thick
• Loosely organized network of cellulose
microfibrils, hemicelluloses, pectins, and
glycoproteins.
• Pectins impart flexability, allowing the cell wall to
expand during cell growth.
• Cellulose microfibrils are synthesised by enzyme
compleses called rosettes, which move across
the membrane along the newly forming fibril.
• A family of proteins called expansins are
important in allowing the cell wall to remain
pliable.
Secondary Cell Wall
• Some cell types stop cell wall synthesis after
forming the primary cell wall.
• Many cells form a multilayered secondary cell wall
after cell growth has ceased.
• The secondary cell wall is composed mainly of
cellulose and lignin.
• These layers are stiff and strong, giving wood much
of its strength.
• Cellulose microfibrils in each layer are parallel, and
those in adjacent layers are at right angles.
• Microtubules in the cell are thought to guide the
rosettes in forming this regular arrangement of
cellulose microfibrils.
Plasmadesmata
• The cell wall poses a barrier to cell cell communication
in plants.
• One part of the solution to this problem is the use of
small water soluble “hormones” which can diffuse
through the cell wall material.
• A second solution is the formation of cytoplasmic
channels through the cell wall of adjacent cells,
allowing communication (like gap junctions in animal
cell, only much larger).
• These openings are called plasmadesmata.
• Tubular (membrane?) structures called desmotubules
are often associated with the plasmadesmata.
• Desmotubules appear to allow continuity of the ER
network of adjacent cells.