Extra cellular matrix biology I

Question 1

What are the functions of the Extracellular matrix

Answer 1

• Provides physical support
• Determines the mechanical and physicochemcial properties of the tissue
• Influences the growth, adhesion and differentiation status of the cells and tissues with which it interacts
• Essential for development, tissue function and organogenesis

Question 2

Define extracellular matrix

Answer 2

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

Question 3

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

Answer 3

Collagen – e.g. collagen type I, type II and III (fibrillar) collagen type IV
Multi-adhesive glycoproteins – fibronectin, fibrinogen and laminins
Proteoglycan - aggrecan, versican, decorin and perlecan

Question 4

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

Answer 4

Collagen type IV Laminin Perlecan

Question 5

A mutation in the gene encoding which ECM compound causes each of the following disease:
Osteogenesis Imperfecta
Marfan's Syndrome
Alport's Syndrome
Epidermolysis bullosa
Congenital Muscular Dystrophy

what part of the ECM does it affect

Answer 5

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)

Affects the matrix protein

Question 6

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

Answer 6

Hurler’s Syndrome – L-alpha-iduronidase Other mucopolysaccharidoses- inability to degrade GAGs (glycosaminoglycans)

Question 7

What are the features of connective tissues?

Answer 7

Rich in ECM.

Contains ECM + component cell e.g. macrophages

Question 8

Give an example of a disease caused by excess deposition of ECM.

Answer 8

Liver fibrosis Lung fibrosis- Silicosis

Kidney Fibrosis- diabetic nephropathy

Question 9

Give an example of a disease caused by excessive loss of ECM

Answer 9

Osteoarthritis

Question 10

Describe the arrangement of collagen fibres in skin, mature bone and eyes and explain its significance.

Answer 10

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

Question 11

What is the structure of a collagen molecule and what is it?

Answer 11

-It is a family of fibrous proteins, found in all multi-cellular organisms. Most abundant protein

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 to the structural integrity of collagen.
-each alpha chain forms a helix, each helix wraps around eachother to form a stiff triple helical structure, indiviual triple helices forms FIBRILS which come together to form COLLAGEN FIBRES.

Question 12

Describe the biosynthesis of collagen.

Answer 12

Collagen is made as procollagen in the endoplasmic reticulum.
•Procollagen has N and C region which are NOT in triple helices.
•Once outside the cell-­the N and C propeptides are removed in fibrillar collagen but remain part of the collagen in most other collagen by extracellular peptidases.
•The collagen is then released and forms fibrils laterally with cross-­‐linkages between collagen molecules in the fibril, providing strength and stability.

Question 13

What is important of the way collagen fibrils are positioned

Answer 13

The alignment of the collagen fibrils determines which directions the tissue can resist tensile force in.

Question 14

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

Answer 14

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 15

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

Answer 15

Hydroxylation is carried out by Prolyl and Lysyl Hydroxylases- this requires Vitamin C and Iron

Question 16

What does a lack of vitamin C mean

Answer 16

Lack of proper collagen hydroxylation which can’t aggregate together properly to form solid fibres ­‐affects tissue stability (scurvy)

Question 17

What are the collagens that don’t form fibrils?

Answer 17

Fibril-associated collagens (e.g. collagen IX+type XII) which is involved in the organisation and size of collagen fibrils

Network forming collagens – e.g. collagen IV (basal lamina). Type IV collagen assembles into a sheet-like network.
the collagen type IV molecules can associate laterally between triple-helical segments as well as head-to head and tail-to tail between the globular domains to give dimers, tetramers and higher order complexes.

Question 18

Describe the composition of Elastic fibres.

Answer 18

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

Question 19

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

Answer 19

Gene mutation in fibrillin 1 Longer arm span than height – long fingers and toes – predisposed to aortic ruptures

Question 20

What is the general structure of elastin?

Answer 20

It consists of a hydrophobic region and an alpha-helical region (which is rich in alanine and lysine. Many lysine side chains are covalently cross-linked.) Changes configuration when stretched and goes back to normal when stress is removed (like rubber band).

Question 21

What are Basement membrane made of

Answer 21

Collage IV and Laminins are the major components. It is a special type of ECM

Question 22

What is diabetic Nephropathy

Answer 22

ECM accumulation

• Impinging on capillaries
• restricts renal filtration leading to renal failure.

Question 23

How do you best describe connective tissues?

What are the functions of basement membranes?

Answer 23

Tissues rich in extracellular matrix with sparse cells.

Separating cells from connective tissue