Extracellular matrix Flashcards
What is the extracellular matrix composed of?
-Collagens
-Elastin
-Proteoglycans
Glycoproteins
What is collagen?
- Major structural protein
- Three peptide 𝛂-chains wrapped around each other
- 3 same homotrimer
- 3 different heterotrimer
- Right hand triple helix
- Glycine essential
- Stabilised by Hydrogen bonds
- Proline and OH-proline provide rigidity and stability
- 3rd amino acids glycine (Gly-X-Y)n
What is type I collagen?
[𝛂1(I)2𝛂2(I)]
What is tendon tensile strength determined by?
Parallel type I collagen fibril bundles - forms lamellae in bone
What is cartilage made of?
Type II collagen and aggrecan
What is the structure of cartilage?
See diagram.
Elastin
Structural protein
Single gene product
Alternating hydrophobic and cross-linking domains
Low turnover
Extremely resilient
Undergoes many cycles of extension and recoil
Fibrillins
Structural proteins
major component of elastic fibres
-large glycoproteins
Beaded string microfibril
Interacts with - elastin, matrix associated glycoproteins, fibulins, latent transforming growth factor beta binding proteins
Regulatory role - TGFbeta storage and activation
Proteoglycans
Diverse family of proteins
contain at least one glycosaminoglycan (GAG) chain
Extracellular Matrix proteoglycans
- hold water in tissues
- Confer material properties; viscoelasticity and resistance to compression
GAGs
occupy large space and form hydrated gels -unbranched polysaccharides -repeating diaccharide units Negatively charged e.g. Hyaluronan Four types of sulphated GAG -Chondroitin Sulphate -Dermatan Sulphate -Heparan Sulphate -Keratan Sulphate Only sulfated bind to proteoglycan
Aggrecan
Major proteoglycan in cartilage -huge multimeric aggregates Link stabolises binding to Hyaluronan highly hydrophobic Huge turgor pressure in tissue - resists compresion
Small Leucine Rich Proteoglycans (SLRP)
Proteoglycans bridge adjacent collagen fibrils -GAG-GAG interactions -maintain separation between fibrils -e.g. corneal transparency
E.g. Lumican - thinner collagen fibrils
e. g. Decorin - proteotypical SLRP
- Binds collagen fibrils at specific sites
- inhibits collagen type I fibrillogenesis in vitro
What are non-sturctural functions of ECM?*
Regulate cell and growth factor activity
Proteoglycans Regulate TGFbeta activity in ECM
Fibroglast growth factor (FGF) signalling
-bind and present ligand (FGF) to receptor
-Receptors dimerise and phosphorylate receptor tyrosine kinase (TK) - transcription regulation
- Activation of RAS/ERK pathway
TGFbeta isolated in ECM by SLRP
Regulation of TGFbeta activity by the ECM