Collagen• Synthesised by VSMC and VEC (perhaps)

– soluble procollagen excreted

– cross linked

– ‘insoluble’ tropocollagen’

– assembled into a fibril (details later)

– fibrils form fibres

• 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

Collagen Fibre Assembly

Collagen fibril10-500 nm

Collagen fibre1-500m

Stabilised by cross links

AssemblyAssemblyProcollagenpeptidase

Chainsassemble

Precursor chain

Procollagen(triple helix

with loose ends)

Collagenmolecule

67 nm

Intracellular

1 2 3 4

Hierarchy of structure

Size range

Visualisation

n.b. 1Å = 0.1nm

Hierarchy of structure

0.87nm

66nm

Glycine every third residue

Collagen molecule

LH helix

RH helix

Type I

Type II

Type IIIdisulphide 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

Chondroitin Sulphate

Keratin Sulphate

Hyaluronate

ProteoglycansProteoglycans

– 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

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

10m

• 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”