Extracellular Matrix

Question 1

What is the extracellular matrix?

Answer 1

Network of protein and carbohydrate filling spaces between cells (deposited by fibroblasts)
Made up of fibrillar and non-fibrillar components

Question 2

What are the functions of the ECM?

Answer 2

Provides cells with physical support
Influences growth, adhesion, differentiation status of the cells with which it interacts (as other tissues are able to bind)
Essential for development, tissue function and organogenesis

Question 3

What are the different molecules found in connective tissue?

Answer 3

Collagens
Multi-adhesive glycoproteins
Proteoglycans

Question 4

What types of collagen are fibrillar?

Answer 4

Types 1-3

Question 5

What type of collagen is found in the basement membrane?

Answer 5

Type 4

Question 6

What molecules are proteoglycans?

Answer 6

Aggrecan
Versican
Decorin
Perlecan (basement membrane)

Question 7

What molecules are multi-adhesive glycoproteins?

Answer 7

Fibronectin
Fibrinogen
Laminins

Question 8

How is collagen able to form tight triple helices?

Answer 8

It has a gly-x-y repeat structure where every third position in the three alpha chains is occupied by glycine
Glycine is the smallest amino acid so it allows the chains to pack very closely together

Question 9

Describe the molecular arrangement of collagen in humans?

Answer 9

28 different collagens encoded by 42 genes
Each collagen molecule comprises of 3 alpha chains, forming a triple helix
Type 1 has 2 different genes and is a heterotrimer(has 2 different chain types) - [a1(I)]2 [a2(I)]
Type 2 and 3 are homotrimers (have only 1 chain type) - [a1(II)]3 and [a1(III)]3

Question 10

Describe collagen biosynthesis

Answer 10

Procollagen is synthesised
The non-collagenous domains at the N and C-termini are removed after secretion of only fibrillar collagen
Protein becomes collagen after secretion and forms fibrils
Cross linkages form to increase tensile strength

Question 11

What are the intracellular steps of fibrillar collagen biosynthesis?

Answer 11

Pro-alpha chain synthesised
Protein undergoes post-translational modification in the Golgi (hydroxylation of lysine and proline, glycosylation of selected hydroxylysines)
Chains self-assemble into helices to form procollagen (can remain in cell or be secreted by a vesicle)

Question 12

What happens after the procollagen is secreted?

Answer 12

Undergoes cleavage of the non-collagenous domains at the N and C-termini to form collagen
Molecules self-assemble into fibrils (10-300nm)
Fibrils aggregate to form fibres (0.5-3 micrometres)

Question 13

Why are cross linkages important?

Answer 13

Provides tensile strength and stability
Involves post-translational modification of lysine and hydroxy-lysine residues
Tissue specific eg. bones require more cross linkage formation as they are under more stress than other tissues
Changes with age- becomes more infrequent as we grow older, so we become weaker

Question 14

Why is the hydroxylation of proline and lysine important?

Answer 14

Contributes to interchain hydrogen formation
If collagen is secreted then the residues can be modified by formation of covalent cross linkages
Prolyl and lysyl hydroxylases require Fe2+ and vitamin C
Deficiency in vitamin C leads to under-hydroxylated collagens with poor stability (scurvy)