Extracellular Matrix Biology I Flashcards
Define extracellular matrix
Complex network of proteins and carbohydrates which forms the insoluble component of the extracellular environment
What are the three main components of the ECM? Give some examples of each.
Collagen – e.g. collagen type IV
Multi-adhesive glycoproteins – fibronectin
Proteoglycan - aggrecan
Which of these substances are only found in the basement membrane?
Collagen type IV
Laminin
Perlecan
A mutation in the gene encoding which ECM compound causes each of the following disease:
Osteogenesis Imperfecta– Type 1 Collagen
Marfan’s Syndrome– Fibrillin 1
Alport’s Syndrome– Type IV Collagen
Epidermolysis bullosa– Laminin 5 (all three chains)
Congenital Muscular Dystrophy– Laminin 2 (alpha 2 chain)
Give an example of a disease that affects ECM catabolism and the protein affected
Hurler’s Syndrome – L-alpha-iduronidase
Give an example of a disease caused by excess deposition of ECM.
Lung Fibrosis, Liver fibrosis
Give an example of a disease caused by excessive loss of ECM
Osteoarthritis
Describe the arrangement of collagen fibres in skin and explain its significance.
Successive layers are at right angles to each other so it can resist tensile force in all directions
What is the structure of a collagen molecule?
It is a stiff triple helix consisting of three alpha chains Every third amino acid is glycine because only glycine is small enough to fit in the inside of the triple helix. The other two amino acids are commonly proline and hydroxyproline, which form interchain hydrogen bonding that contributes ot the structural integrity of collagen
Describe the biosynthesis of collagen.
Collagen is synthesised as pro-collagen which has two protruding propeptides, one at each end, which aren’t in triple helical form Once it leaves the cell, the propeptides are cleaved and the collagen is able to form cross-linkages with other collagen molecules to form collagen fibrils
What is the importance of hydroxylation of proline and lysine in collagen structure?
It allows interchain hydrogen bonding that contributes to the structural integrity and stability of the collagen fibre Lysine and hydroxylysine is also modified in the formation of covalent cross-linkages after the collagen is secreted – this helps provide tensile strength and stability
What two other substances are needed for hydroxylation of proline and lysine?
Vitamin C and Iron
What are the collagens that don’t form fibrils?
Fibril-associated collagens (e.g. collagen IX) which is involved in the organisation and size of collagen fibrils
Network forming collagens – e.g. collagen IV (basal lamina)
Describe the composition of Elastic fibres.
They consist of an elastin core and microfibrils around the outside that are rich in fibrillin
What causes Marfan’s syndrome and what are some clinical features of Marfan’s Syndrome?
Gene mutation in fibrillin 1
Longer arm span than height – long fingers and toes – predisposed to aortic ruptures
