Week 3- Extracellular Matrix

Question 1

What is the extracellular matrix?

Answer 1

A complex of macromolecules deposited by cells, contains fibrillar and non fibrillar components

Question 2

What is the function of the extracellular matrix?

Answer 2

Mechanical stability and support, also influences cell behaviour (growth, differentiation, status of tissue)

Question 3

What do connective tissues contain?

Answer 3

Collagen, adhesive glycoproteins, proteoglycans, cellular components. Differ in what they contain and orientation of collagen eg vitreous humour vs tendon vs cartiledge

Question 4

Describe the structure of collagen

Answer 4

Made of 3 alpha chains that wind together to form a helix, every 3rd amino acid is glycine as its the smallest amino acid, a fibrous protein. It provides tensile strength and stability

Question 5

How many types of collagen are there and how do they differ?

Answer 5

Type 1- heterodimer, contains chains from 2 different genes

Type 2 & 3- homodimer, contains chains from only 1 gene

Question 6

What are some post translational modifications undergone by collagen?

Answer 6

Hydroxylation of proline and lysine, lysine hydroxylation allows intramolecular cross linkages (only after collagen is secreted)

Question 7

What happens to collagen if someone has scurvy?

Answer 7

A lack of vitamin C means hydroxylation cannot occur causing low tissue stability due to less cross links

Question 8

Describe the biosynthesis of collagen

Answer 8

Collagen chains are first manufactured as longer pro alpha chains that fold into triple helical procollagen molecules before release.

Question 9

How do collagen fibers assemble?

Answer 9

Tropocollagen molecules are staggered to form fibrils. Their parallel nature means they resist force in one direction, making them stronger

Question 10

What symptoms of Ehler’s Danlos syndrome is related to skin?

Answer 10

A mutation in collagen can result in stretchy and loose skin

Question 11

What is special about type IV collagen?

Answer 11

It doesn’t form membranes

Question 12

What is the basement membrane?

Answer 12

A membrane that underlies epithelia, surround smooth muscle + peripheral nerves + fat cells. In kidneys it forms the glomerular basement membrane

Question 13

How does diabetic neuropathy affect basement membranes?

Answer 13

There is a thickening of the basement membrane due to extra deposition of extracellular matrix restricting renal filtration and leading to kidney failure

Question 14

What happens in Alport syndrome?

Answer 14

Splitting of the glomerular basement membrane causes loss of kidney function and hearing loss

Question 15

Describe the structure of elastic fibers

Answer 15

Contain a core of elastin (a protein made of 2 alternating regions- hydrophobic and alpha helical, the latter of which is rich in alanine and lysine with lysine forming covalent crosslinks) and microfibrils rich in the protein fibrillin

Question 16

What happens in Marfans syndrome?

Answer 16

A mutation in the gene for fibrillin 1 protein causes skeletal and ocular problems

Question 17

What are proteoglycans?

Answer 17

A core protein to which are attached GAG chains

Question 18

Describe the structure of GAG chains

Answer 18

They are made of real eating disaccarides of which at least one is an amino sugar (a sugar where the hydroxyl group is replaced by an amino group). Many are sulphated or carboxyalted giving them a negative charge so water moves into the ECM. Swelling pressure is negated by collagen fiber tension.

Question 19

What are the 4 main groups of GAG chains

Answer 19

Hyaluron
Dermatan phosphate
Keratan phosphate
Heparan phosphate

Question 20

Describe the structure of hyaluron

Answer 20

A carbohydrate chain without any core proteins, can undergo lots of polymerization and become large so it has a high viscosity

Question 21

Describe the structure of aggrecan

Answer 21

Major component of cartilage in the ECM, GAGs are very highly sulphated so high negative charge and draws lots of water in

Question 22

What happens in osteoarthritis?

Answer 22

Erosive degradation of ECM leading to loss of cartiledge cushioning. As age increases aggrecan is cleaved by aggrecanases

Question 23

What happens in fibrotic disease

Answer 23

Excessive production of fibrous tissue