Extracellular Matrix

Question 1

Give some examples of specialsed ECM

Answer 1

Bone
Keratin → hair, fingernails
Tendons
Cornea

Question 2

What is the ECM

Answer 2

Extracellular meshwork of proteins and hydrated, macromolecules

Question 3

What is the function of the ECM

Answer 3

Migration
Tissue integrity and cell shape
Proliferation (anchorage dependent growth)
Differentiation

Question 4

Give 2 examples of fibrous proteins ECM components

Answer 4

Collagens
Elastin

Question 5

Give 2 examples of adhesion protein ECM components

Answer 5

Fibronectin
Laminin

Question 6

Give 2 examples of hydrated macromolecules ECM components

Answer 6

Glycosaminoglycans (Gags)
Proteoglycans (Proteins + Gags)

Question 7

What are the characteristics of collagen

Answer 7

Triple helical protein
Glycine-proline-hydroxyproline triplet repeats
= Strands can self assemble into triple helix
3 alpha chains
Tensile strength
Produced mainly by fibroblasts and epithelial cells

Question 8

Describe collagen synthesis

Answer 8

multi-step, mostly driven by self-assembly
Modification, glycosylation (hydroxylation of residues)
Enzymes responsible for hydroxylation use vitamin C as a cofactor
(Low levels of vitamin C = problems e.g scurvy)

Question 9

What is fibrilin?

Answer 9

Elastin laid down over microfibril scaffold of fibrillin

Question 10

Describe GAG (Glycosaminoglycans)

Answer 10

Disaccharide chains, 70-200 units long
Highly charged → good at holding water due to its polarity

Question 11

Describe hyaluronan complexes

Answer 11

Very large → over 100 mil daltons
Highly charged
= Good at holding water and filling space
Aggrecan - protein core
Sugar chains substituted on )highly sulfated
Aggrecan linked to hyaluron backbone by link proteins

Question 12

Describe laminin

Answer 12

• Adhesion protein
• Cruciform structure
• Self assembly - cross linked mat
• Nidogen → matrix proteins will bind to other types of matrix proteins to build a network
• Binding sites for integrins

Question 13

Describe fibronectin

Answer 13

Adhesion protein:
- Disulfide cross link sites → for covalent associations = strong struc
- Other domains drive non-covalent association
- Both of these ensure fibronectin can form a network
- Can bind to other matrix proteins → especially collagen
- contains RGD sequence (binding sites for integrins)

Question 14

Describe integrins

Answer 14

Heterodimer
Divalent cation →from strong ionic bond with RGD sequence and aspartic residues in integrin
Removal of cations causes cells to detach

Question 15

What are the components of focal adhesion?

Answer 15

• integrins (transmembrane receptors)
• connection to cytoskeleton (= doesn’t rely on a single bond)
• signalling

Question 16

Give 2 examples of integrin-related pathologies

Answer 16

aII3B3-Integrin
- Integin in platelets → binds to fibrinogen to clot blood
- Glazmann’s thrombasthenia (bleeding gums, nose bleeds)

B2-Integrin
- Integrin involved in immune cells
- Leukocyte Adhesion Deficiency (LAD) syndrome
Not a mutation in protein but impaired expression of integrin
= Patient susceptible to infection

Question 17

What do fibrous proteins provide to the ECM?

Answer 17

e.g collagen and elastin
- provide structural integrity

Question 18

What are integrins?

Answer 18

transmembrane receptors that mediate adhesion