This document discusses the extracellular matrix (ECM), including its composition, functions, and role in health and disease. The ECM is made up of three main components - glycans, proteoglycans, and fibrous proteins. It provides structural support and helps with cell adhesion. Diseases associated with abnormalities in ECM components include scurvy resulting from vitamin C deficiency impairing collagen formation, osteogenesis imperfecta causing brittle bones from collagen gene mutations, and Marfan syndrome stemming from mutations in the gene coding for fibrillin in the ECM protein elastin. The ECM plays an important role in both health and a variety of diseases.

1. EXTRACELLULAR MATRIX
• Components and functions
• Role of ECM in health and disease

2. AGENDA
◎ What is extracellular matrix?
◎ Composition of ECM
◎ Functions of ECM
◎ Associated diseases
◎ Summary
◎ Approximate time: 35 – 40 minutes
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6. Cells Tissues Organs Systems
CONNECTIVE TISSUE? EXTRACELLULAR MATRIX

7. Substantial part of tissue volume: Extracellular space
largely filled by macromolecules of ECM
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Generally secreted by cells of the tissue
Assembled into a meshwork
Different
functions in
different
tissues

8. Different cells have different proportions of cellular and
extracellular components
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Epithelial cells:
More cellular
components,
less ECM
Connective tissue:
Less cellular
components, more
ECM
Physical
characteristics
different:
Blood is
liquid,
collagen is
spongy

9. ECM IS MADE OF THREE COMPONENTS
ECM
Glycans
Glycosaminoglycans
Proteoglycans
Fibrous proteins
Collagen
Elastin
Adhesive proteins
Fibronectin
Laminin
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10. PROTEOGLYCANS
◎ Aggregates of GAGs (mucopolysaccharides) and
proteins (chondroitin sulphate most common)
○ Negative charge, repel each other (slippery)
○ Water fills the ECM, repels the forces of tissue
compression (resists compression)
○ GAG + collagen in cartilage of big joints (water
squeezed out during compression, once the pressure is released,
water rushes back) - Resilience
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11. FIBROUS PROTEINS
◎ Structural components (secondary structure)
◎ Collagen and Elastin
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• Most abundant protein
• Main protein in bone,
skin, and tendon
• ECM as a gel like
substance, provides
support and strength
• 28 different types
(90% is type 1 to 4)
• Mainly seen in skin, arteries, and
lungs
• Contains less hydroxyproline than
collagen
• No carbohydrates in elastin

12. CELL ADHESION MOLECULES
◎ Cell to cell and cell to ECM adhesions mediated by
plasma membrane anchored proteins (cell adhesion molecules)
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Forms junctions:
• Tight/occluding
• Anchoring/desmosomes
• Gap/communicating
Transmembrane proteins
• Extend from cytoplasm through
plasma membrane into EC space
• Binds to specific ligands
• Cadherins
• Selectins
• Immunoglobulin superfamily
• Integrins
• Holds cells together,
maintains cell integrity
• Needs calcium
Important in WBC
migration to sites of
inflammation
• Structural similarity to
immunoglobulins
• May be involved in
immunological functions
Cell to cell and cell to
ECM adhesions
Weaker interaction

13. DISEASES ASSOCIATED WITH FIBROUS PROTEINS
◎ Scurvy
◎ Osteogenesis imperfecta
◎ Ehlers – Danlos syndrome
◎ Marfan syndrome
◎ α1 Antitrypsin deficiency
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14. SCURVY
◎ Deficiency of Vitamin C
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Impaired hydroxylation of
proline and lysine
Defective pro-α chains
Lack of stable triple helix
Less normal functional
collagen
Fragile blood vessels
Slow wound healing
Gingival bleeding
Tooth loss
ACQUIRED

15. OSTEOGENESIS IMPERFECTA
◎ Brittle bone disease
◎ Any of the many mutations in collagen gene
◎ Currently, eight subtypes identified
◎ Most common is Type 1, most lethal is Type 2
◎ Most are AD
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INHERITED

16. EHLERS DANLOS SYNDROME
◎ Uncommon
◎ Inherited defects in the structure, production, or
processing of collagen
◎ Six major types, all affects joints and skin
◎ Most are AD
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17. MARFAN SYNDROME
◎ Mutation in the gene coding for Fibrillin -1
(component of elastin)
◎ Most affected organs
◎ Long limbs and digits
◎ Tall stature
◎ Scoliosis
◎ Myopia, astigmatism
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18. α1 ANTITRYPSIN DEFICIENCY
◎ Elastin is involved (like Marfan)
◎ Inappropriate destruction of lung
elastin by elastase
◎ Manifests as emphysema
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Elastase
α1 Antitrypsin

19. CELL ADHESION AND DISEASE
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REDUCED ADHESION INCREASED ADHESION
Cancers
Leukocyte adhesion
defects
Pemphigus
Asthma
Rheumatoid arthritis
As receptor
for viruses
CAUSES DISEASES
Fatty streak in
atherosclerosis