3. Extracellular matrix I

Question 1

Define extracellular matrix

Answer 1

Complex network of proteins and carbohydrates filling spaces between cells
Comprises fibrillar and non-fibrillar components

Question 2

List 4 functions of the ECM

Answer 2

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

Question 3

What type of tissue is rich in ECM?

Answer 3

Connective tissue

Question 4

What are the 3 main components of the ECM? Give examples of each.

Answer 4

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

Question 5

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

Answer 5

Collagen type IV
Laminin
Perlecan

Question 6

Give 5 examples where gene mutations affect ECM matrix proteins

Answer 6

Osteogenesis imperfecta: Type I collagen
Marfan’s syndrome: Fibrillin 1
Alport’s syndrome: Type IV collagen (alpha 5)
Epidermolysis Bullosa- Laminin 5 (in all 3 chains)
Congenital Muscular Dystrophy- Laminin 2 (alpha 2 chain)

Question 7

Give 2 examples where gene mutations affect ECM catabolism

Answer 7

Hurler’s syndrome: L-alpha-iduronidase

Other “mucopolysaccharidoses” (inability to degrade GAGs)

Question 8

Give 3 fibrotic disorders due to excessive ECM deposition

Answer 8

Liver fibrosis: cirrhosis
Kidney fibrosis: diabetic nephropathy
Lung fibrosis: silicosis

Question 9

Give an example of a disorder due to excessive loss of ECM

Answer 9

Osteoarthritis

Question 10

Different types/ orientations of collagen give connective tissue varied properties

Answer 10

Tendon and skin: Tough and flexible
Bone: hard and dense
Cartilage: Resilient and shock-absorbing

Question 11

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

Answer 11

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

Question 12

Variability of collagen

Answer 12

28 collagen types in humans
42 genes encoding collagens
Each collagen molecule comprises 3 alpha chains, forming a triple helix.
Can be composed of one or more different alpha chains

Question 13

What is the structure of a collagen molecule?

Answer 13

Stiff triple helix consisting of 3 alpha chains
Every 3rd AA is glycine because only glycine is small enough to fit in the inside of the triple helix.
The other 2 AAs are commonly proline and hydroxyproline, which form interchain hydrogen bonding that contributes to the structural integrity of collagen

Question 14

How long is each alpha chain in fibrillar collagen and what does this form?

Answer 14

1000 AAs long

Forms left-handed helix

Question 15

Describe the biosynthesis of collagen.

Answer 15

Synthesised as pro-collagen which has 2 protruding pro-peptides, 1 at each end, which aren’t in triple helical form
In fibrillar collagen after secretion, pro-peptides are cleaved, so collagen can form cross-linkages with other collagen molecules to form collagen fibrils
Pro-peptides remain part of the collagen in most other types of collagen

Question 16

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

Answer 16

Allows interchain hydrogen bonding that contributes to the structural integrity and stability of the collagen fibre
Lysine and hydroxylysine are also modified in the formation of covalent cross-linkages after the collagen is secreted – this helps provide tensile strength and stability

Question 17

What 2 other substances are needed for hydroxylation of proline and lysine?

Answer 17

Vitamin C

Iron

Question 18

What does vitamin C deficiency result in?

Answer 18

Underhydroxylated collagens

Detrimental to tissue stability (scurvy).

Question 19

How is collagen arranged in tendons?

Answer 19

Parallel bundles

Question 20

What are the collagens that don’t form fibrils?

Answer 20

Fibril-associated collagens (e.g. collagen IX) which is involved in the organisation of collagen fibrils
Network forming collagens (e.g. collagen) in basement membranes

Question 21

Describe collagen type IV assembly

Answer 21

Assembled into a sheet-like network

= essential component of basement membranes

Question 22

Describe the composition of Elastic fibres.

Answer 22

Elastin core

Microfibrils around the outside that are rich in fibrillin

Question 23

What are elastic fibres important for?

Answer 23

Elasticity of tissues e.g. skin, blood vessels

Question 24

How is the extent of stretching limited?

Answer 24

Collagen and elastin fibres are interwoven

Question 25

What does the integrity of elastic fibres depend on?

Answer 25

Microfibrils

Question 26

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

Answer 26

Gene mutation in fibrillin 1
Longer arm span than height
Long fingers and toes
Predisposed to aortic ruptures

Question 27

What is the general structure of elastin?

Answer 27

Consists of hydrophobic regions and alpha-helical regions (rich in alanine and lysine)
Many lysine chains are covalently cross-linked

Question 28

What are basement membranes?

Answer 28

Highly specialised ECMs containing distinct spectra of collagens, glycoproteins and proteoglycans.
Flexible, thin mats underlying epithelial sheets, tubes, muscle, fat and peripheral nerve cells
Regulate tissue function

Question 29

What are basement membranes also known as?

Answer 29

BMs

Basal laminae

Question 30

What does the BM in the kidney act as?

Answer 30

Highly selective filter