Download EXTRACELLULAR MATRIX

EXTRACELLULAR MATRIX
LECTURE OBJECTIVES
At the end of lecture the student should be able to;
1. Define Extra-cellular matrix
2. Describe the structure of proteins, carbohydrates and mineral content of ECM.
3. Describe the functions of various molecules of ECM.
4. Describe the various forms of Extra-cellular matrix (intercellular space, subcutaneous
tissue, cartilage, bone) w.r.t. the variations in protein carbohydrates and mineral contents.
EXTRACELLULAR MATRIX (ECM)
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COMPOSED OF:
– Matrix:
The base on which the structure develops
– Extracellular: Outside the cells/ in between the cells in a tissue
DEFINITION
– A substance containing collagen, elastin, proteoglycans, glycosaminoglycans, and
fluid, produced by cells and in which the cells are embedded. The matrix secreted
by chondroblasts, for example, is responsible for the properties of cartilage.
DEFINITIONS
Extracellular constituents; All of the constituents of the body outside the cells;
include water, electrolytes, protein, glucose, enzymes, hormones.
• Extracellular fluid; All of the body fluid lying outside the cells. Includes intravascular
fluid or plasma and the interstitial fluid. That part of the extracellular fluid that is in
special cavities which have special characteristics, e.g. synovial fluid, urine, aqueous
humor of eye, are called transcellular fluids.
• Extracellular matrix The network of proteins and carbohydrates that surround a cell or
fill the intercellular spaces.
• Extracellular/Intercellular space The space outside the cell.
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EXTRACELLULAR MATRIX (ECM)
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Secreted by cells therefore reflect the properties of the particular tissue
– Bone matrix The intercellular substance of bone, consisting of collagenous
fibers, ground substance, and inorganic salts.
– Cartilage matrix The intercellular substance of cartilage, consisting of cells and
extracellular fibers embedded in an amorphous ground substance.
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Skin matrix Contains more elastic fibers along with glycosaminoglycans and
ground substance
ECM: FUNCTIONS
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Mechanical support for cells and tissues.
Influences cell shape, movement, development and differentiation.
Coordinates cellular functions through cell to cell signaling with adhesion receptors
(integrin).
Reservoir for extracellular signaling molecules
ECM: COMPONENTS
1. Fibrous elements
– Collagen, elastin
2. Link proteins
– Fibronectin, laminin
3. Space filling molecules
– Proteoglycans and glycosaminoglycans.
ECM: FIBROUS ELEMENTS
COLLAGEN
Most abundant animal protein
• insoluble tensile fibers
• Basic structure is Gly-X-Y
• Special amino acids hydroxylated lysine and proline
• 19 types of collagen
• Modified/ different as per the requirements
– Bones
– Cartilage
– Subcutaneous tissue
– Articular capsules
SYNTHESIS OF COLLAGEN
TYPES OF COLLAGEN
Type Tissue
Type Tissue
I
Most connective tissues, including II
bone
Cartilage, vitreous humor
III
Extensible connective tissues such IV
as skin, lung, and the vascular
system
Basement membranes
V
Minor component in tissues
containing collagen I
Most connective tissues
VI
VII
Anchoring fibrils
VIII
Endothelium, other tissues
IX
Tissues containing collagen II
X
Hypertrophic cartilage
XI
Tissues containing collagen II
XII
Tissues containing collagen I
XIII Many tissues
XIV Tissues containing collagen I
XV
XVI Many tissues
Many tissues
XVII Skin hemidesmosomes
XVIII Many tissues (eg, liver, kidney)
XIX Rhabdomyosarcoma cells
ECM: FIBROUS ELEMENTS ELASTIN
Fibrous protein
Extensibility and elastic recoil
Large amount in lungs, large arterial blood vessels, and some elastic ligaments
Small amounts in skin and ear cartilage
Major cross-links are the desmosines, which result from the condensation of four lysine
residues to form a tetra-functional crosslink.
• Highly insoluble, stable and a very low turnover rate.
• Random coil conformations that permit the protein to stretch and subsequently recoil
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DIFFERENCES
BETWEEN COLLAGEN AND ELASTIN
S. No. Collagen
Elastin
1
2
Many different genetic types
Triple helix
One genetic type
No triple helix; random
coilconformations permitting stretching
3
(Gly-X-Y)n repeating structure
No (Gly-X-Y)n repeating structure
4
Presence of hydroxylysine
No hydroxylysine
5
Carbohydrate-containing
No carbohydrate
6
Intramolecular aldol cross-links
Intramolecular desmosine cross-links
7
Presence of extension peptides
during biosynthesis
No extension peptides present
during biosynthesis
CLINICAL CORRELATES
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Ehlers-Danlos syndrome
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Hyperextensibility of the skin, abnormal tissue fragility,
and increased joint mobility
Alport syndrome
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Hematuria, and patients may eventually develop endstage renal disease
Epidermolysis bullosa
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Skin breaks and blisters as a result of minor trauma
Affect gums, subcutaneous hemorrhages, and poor
wound healing
LINK PROTEINS: FIBRONECTIN
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Major glycoprotein of the ECM
Also found in a soluble form in plasma
Two identical subunits joined by two disulfide bridges
Three types of repeating motifs (I, II, and III)
Organized into functional domains
Bind with heparin and fibrin, collagen, DNA, and cell surfaces
FIBRONECTIN
LINK PROTEINS: LAMININ
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Major protein of basal laminas and glomerular membrane
Three distinct elongated polypeptide chains (A, B1, and B2) linked together to
form an elongated cruciform shape
Binding sites for type IV collagen, heparin, and integrins on cell surfaces.
LINK PROTEINS: FIBRILIN
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Large glycoprotein
Structural component of microfibrils
Secreted by fibroblasts and incorporated into the insoluble microfibrils
Provide a scaffold for deposition of elastin.
found in the zonular fibers of the lens, in the periosteum, and associated with elastin
fibers in the aorta
CLINICAL CORRELATE: MARFAN SYNDROME
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Inherited disease affecting connective tissue
Autosomal dominant trait
Affected tissues
– eyes (dislocation of the lens, known as ectopia lentis)
– Skeletal system (most patients are tall and exhibit long digits [arachnodactyly]
– Joints (hyperextensibility)
– cardiovascular system (weakness of the aortic walls, dilation of the ascending
aorta)
SPACE FILLING MOLECULES: PROTEOGLYCANS &
GLYCOSAMINOGLYCANS GAGS
Proteoglycans are proteins that contain covalently linked.
Core proteins are covalently bound to GAGs.
Seven types of GAGs: hyaluronic acid, chondroitin sulfate, keratan sulfates I and II,
heparin, heparan sulfate, and dermatan sulfate.
• GAG is an unbranched polysaccharide made up of repeating disaccharides
• One component of which is always an amino sugar and the other is mostly a uronic
acid
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PROTEOGLYCANS & GLYCOSAMINOGLYCANS (GAGS)
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Negatively charged
Attract and retain water
Provide medium for ion, nutrient and mineral exchange
PROTEOGLYCANS & GAGS
Gags
Sugars
Location
Hyaluronic Acid GIcNAc,
GlcUA
Synovial fluid, vitreous humor, loose
connective tissue
Chondroitin
Sulfate
associated with HA via link proteins
Cartilage, bone, cornea
GaINAc,
GlcUA
Keratan sulfate I GlcNAc, Gal
Cornea
Keratan sulfate II GlcNAc, Gal
Loose connective tissue
Heparin
Mast cells
GlcN, IdUA
Heparan sulfate GlcN, GlcUA Skin fibroblasts, aortic wall
Dermatan Sulfate GalNAc, IdUA Wide distribution
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