Extracellular Matrix

Extracellular Matrix

1. Functions

   • tissue integrity
   • cell shape
   • microbe defense
   • proliferation
   • migration
   • differentiation
   • scaffold
     • tissue engineering

2. fibrous mesh

   • fibrous proteins
     • elastin
     • collagen
   • adhesion proteins
     • laminin
       • basal laminae
         • axon promoting
     • fibronectin
       • bind cells to collagen
         • RGD protein
   • hydrated macromolecules
     • GAGs
       • glycosaminoglycans
       • proteoglycans
         • 4 sugars tetrasaccharide
         • GAG + protein
       • hyaluration

3. collagen

   • most
   • 20-40 varients
   • triple helices
     • 3 alpha chains
   • fibroblast family/epithelial cells
   • synthesis
     • modified chain into ECM
       • aggregation of collagen fibrils
         • fibre
     • scar tissue
       • collagen tension
         • wound
           • fibroblast proliferate
         • scurvery no collagen
           • vitmin c deficiency

4. elastic

   • all connective tissue
   • tropoelastin to elastin
     • lysyl oxidase
       • implicated in metastasis
   • with microfibrils of fibrillin forming fibres
   • Marfan's syndrome
     • FBN1 gene - in blood vessels

5. ground substance

   • no proteinascious
   • GAGs
     • disaccharide chains
     • dermatan sulphate
     • hyaluronic acid
       • non-sulphated
       • secreted as strand
         • repeated disaccharide

6. proteoglycan complexes

   • hyaluronic acid
     • linked to proteins and proteoglycans
       • aggrecan
   • long links
   • roles
     • cushioning
       • bind to H2O/expand
         • cartilage/tendon
     • packing
       • embryogenesis empty spaces
         • 85-90%
           • H2O in embryo
       • hyaluronidase
         • breaks down hyaluronic acid
           • can move more freely
     • filtering
       • restricts flow/large molecules
         • cant get through hydrated mol
     • signal binding
       • GAGs cell surface
       • wait in extra cell space

7. structural glycoproteins

   • protein + sugar
   • integrins
     • ECM receptors
       • link ECM and cytoskeleton
     • Glanzmann's thrombosthenia
       • low integrin expression on blood platelets
         • binds fibrinogen
           • haemophilia

8. Gargolysin-Hurlers' syndrome

   • alpha-L-iduronidase deficiency
     • dermaton/heparon sulphate accumulation
       • in tissues
       • GAG type molecules in EC space