Extracellular Matrix Biology I

Question 1

Define extracellular matrix

Answer 1

Complex network of proteins and carbohydrates which forms the insoluble component of the extracellular environment

Question 2

What are the three main components of the ECM? Give some examples of each.

Answer 2

Collagen – e.g. collagen type IV
Multi-adhesive glycoproteins – fibronectin
Proteoglycan - aggrecan

Question 3

Which of these substances are only found in the basement membrane?

Answer 3

Collagen type IV
Laminin
Perlecan

Question 4

Give an example of a disease that affects ECM catabolism and the protein affected

Answer 4

Hurler’s Syndrome – L-alpha-iduronidase

Question 5

Describe the arrangement of collagen fibres in skin and explain its significance.

Answer 5

Successive layers are at right angles to each other so it can resist tensile force in all directions

Question 6

What is the structure of a collagen molecule?

Answer 6

• 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

Question 7

Describe the biosynthesis of collagen.

Answer 7

• first procollagen
• N and D terminal propeptides
• procollagen is then hydroxylated and glycosylated
• the terminal propeptides are cleaved
• the collagen forms fibrils

Question 8

What is the importance of hydroxylation of proline and lysine in collagen structure?

Answer 8

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

Question 9

What two other substances are needed for hydroxylation of proline and lysine?

Answer 9

Vitamin C and Iron

Question 10

What are the collagens that don’t form fibrils?

Answer 10

• 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)

Question 11

Describe the composition of Elastic fibres.

Answer 11

They consist of an elastin core and microfibrils around the outside that are rich in fibrillin

Question 12

What causes Marfan’s syndrome and what are some clinical features of Marfan’s Syndrome?

Answer 12

Gene mutation in fibrillin 1

- Longer arm span than height – long fingers and toes – - predisposed to aortic ruptures

Question 13

What is the general structure of elastin?

Answer 13

It consists of a hydrophobic region and an alpha-helical region

Question 14

what are main functions of the ECM?

Answer 14

• physical support
• mechanical properties
• growth
• development

Question 15

what does the connective tissue do?

Answer 15

• separates yet holds together the other tissues

Question 16

what does the connective tissue contain?

Answer 16

collagen, macrophages and fibroblasts, ECM, mast cells, , proteoglycans, glycoproteins

Question 17

what do the following diseases have a mutation of?

osteogenesis imperfecta 
Marfan's 
alports 
epidermolysis bullosa 
congenital muscular dystrophy

Answer 17

osteogenesis imperfecta : T1 collagen 
Marfan's : fibrillin 1 
alports :  IV collagen 
epidermolysis bullosa :  Laminin 5 
congenital muscular dystrophy : Laminin 2

Question 18

what does liver fibrosis cause
what doe kidney fibrosis cause
what does lung fibrosis form

Answer 18

liver fibrosis cause - cirrhosis

kidney fibrosis cause - diabetic nephropathy

lung fibrosis form - silicosis

Question 19

what does loss of ECM cause?

Answer 19

osteoarthritis

Question 20

what is the basement membrane?

Answer 20

• flexible thin mats of ECM underlying the epithelial sheets
• might act as a selective filter