Collagen - PowerPoint PPT Presentation

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collagen n.
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Collagen

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  1. Collagen • Synthesised by VSMC and VEC (perhaps) • soluble procollagen  excreted • cross linked • ‘insoluble’ tropocollagen’ • assembled into a fibril (details later) • fibrils form fibres

  2. Collagen • Most abundant protein in body (25-30% of all protein) • >20 distinct forms • Types I, III, IV, V, VI, VIII most common in CV system • Types I, III form fibres –major structural elements • synthesized by fibroblasts and SMCs • Type IV forms a porous network (basement membrane) for endothelial cells to attach to (synthesized by ECs) • Types V, VI: provides thin covering over SMCs

  3. Collagen • Fibres are folded at physiologic loads • Half-life in CV system on order of 15-90 days • Degraded by blood borne enzymes • Proteases (matrix metalloproteinases, MMPs) • released by macrophages • De-natured by heat (approx 60°C)

  4. Collagen Fibre Assembly 1 2 3 4 Chains assemble Procollagen peptidase Assembly Assembly 67 nm Precursor  chain Procollagen (triple helix with loose ends) Collagen molecule Collagen fibril 10-500 nm Collagen fibre 1-500m Intracellular Stabilised by cross links

  5. Hierarchy of structure Visualisation n.b. 1Å = 0.1nm Size range


  6. Hierarchy of structure

  7. Collagen molecule 66nm LH helix 0.87nm RH helix Glycine every third residue

  8. Type I Type II Type III disulphide bonds

  9. Collagen aggregate structure Fibre forming (Types I,II,III,V,K) Membranous (Type IV)

  10. Stagger of collagen molecules in a fibril Total length = 4.4D where D is the length of the striation

  11. Tendon Skin

  12. Ground substance • Mucopolysaccharides (glycosaminoglycans) • Water • Approx 3% of arterial wet weight • Viscous but not elastic

  13. Proteoglycans Proteoglycans • Proteins with covalently bound glycosaminoglycans (linear polymers with disaccharide units) along length • Can hold 50x their dry weight in water • Resistant to compression due to high water content Chondroitin Sulphate Keratin Sulphate Hyaluronate

  14. Fibronectin • Glycoprotein synthesized by fibroblasts, SMCs, ECs • Mediates cellular interactions and migrations (e.g. guides macrophages into wound areas) • Binds fibroblasts to collagen substrates • Crosslinks and stabilizes other components of ECM - • patterns of FN similar to patterns of microfilaments 50m

  15. Laminin • Found primarily in the basal laminae-specialized thin (50 nm) sheets of ECM material separating endothelial cells from ECM • Maintains tissue organization • Acts as “molecular sieve” 10m