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. 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 Collagen

3. 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) Collagen

4. Collagen Fibre Assembly Collagen fibril 10-500 nm Collagen fibre 1-500  m Stabilised by cross links Assembly Procollagen peptidase Chains assemble Precursor  chain Procollagen (triple helix with loose ends) Collagen molecule 67 nm Intracellular 1234

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

6. Hierarchy of structure

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

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. Chondroitin Sulphate Keratin Sulphate Hyaluronate 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

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 10  m 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”