Transcript Reflections
Collagen • Synthesised by VSMC and VEC (perhaps) – – – – – soluble procollagen excreted cross linked ‘insoluble’ tropocollagen’ assembled into a fibril (details later) fibrils form fibres 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 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) Collagen Fibre Assembly 1 2 Chains assemble Procollagen peptidase 3 4 Assembly Assembly 67 nm Precursor chain Procollagen (triple helix with loose ends) Intracellular Collagen molecule Collagen fibril 10-500 nm Collagen fibre 1-500m Stabilised by cross links Hierarchy of structure Visualisation n.b. 1Å = 0.1nm Size range Hierarchy of structure Collagen molecule 66nm LH helix RH helix 0.87nm Glycine every third residue Type I Type II Type III disulphide bonds Collagen aggregate structure Fibre forming (Types I,II,III,V,K) Membranous (Type IV) Stagger of collagen molecules in a fibril Total length = 4.4D where D is the length of the striation Tendon Skin Ground substance • • • • Mucopolysaccharides (glycosaminoglycans) Water Approx 3% of arterial wet weight Viscous but not elastic 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 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 50m Laminin • Found primarily in the basal laminaespecialized thin (50 nm) sheets of ECM material separating endothelial cells from ECM • Maintains tissue organization • Acts as “molecular sieve” 10m