Extracellular Matix

Question 1

What are the functions of the Extracellular matrix?

Answer 1

Physical support
Determines mechanical and physiochemical properties of tissue
Influences growth, differentiation and adhesion of different tissues

Question 2

What are the components of connective tissue?

Answer 2

Collagen fibres
Macrophages, fibroblasts etc.
Multi-adhesive glycoproteins (fibrinogen/laminins)
Proteoglycans (Aggrecan, versican, decorin)

Question 3

What is connective tissue?

Answer 3

Seperates and holds together other tissues.

Contains few cells and lots of ECM

Question 4

What matrix protein gene mutation does Osteogenesis imperfecta effect?

Answer 4

T I Collagen

Question 5

What matrix protein gene mutation does Marfan’s effect?

Answer 5

Fibrillin 1
Mutation in fibrillin-1 leads to loss of integrity of elastic fibres because fibrillin has not formed properly; tall and skinny with predisposition to aortic rupture

Question 6

What three disorders are due to excessive ECM deposition?

Answer 6

Cirrhosis - Liver fibrosis
Diabetic neuropathy - kidney fibrosis
Silicosis - Lung fibrosis

Question 7

What disease results from excessive loss of ECM?

Answer 7

Osteoarthritis

Question 8

What disease is caused by mutations affecting ECM catabolism?

Answer 8

Hurler’s syndrome

Question 9

What percentage of body weight is collagen?

Answer 9

25%

Question 10

How many types of collagen are there in humans, and how many genes code for them?

Answer 10

28 by 42 genes

Question 11

What is the molecular structure of collagen?

Answer 11

Three alpha chains forming left-handed triple helix

Question 12

What is every third amino acid in collagen and why?

Answer 12

Glycine, as its the only one small enough to occupy the interior

Question 13

What is Type I collagen made of? How is this written?

Answer 13

2x alpha 1 and 1x alpha 2

[a1(I)]2 [a2(I)]

Question 14

What is the organisation of collagen?

Answer 14

Trip helix forms 10-30nm fibril, arranged into 0.5-3um fibres

Question 15

Describe collagen biosynthesis

Answer 15

Procollagen synthesised first, with N and D terminal propeptides at each end; these are cleaved upon release from cell, allowing collagen to form fibrils; covalent cross links then form between fibrils to form fibres

Question 16

What does Vit C deficiency result in?

Answer 16

Underhydroxylated Collagens - scurvy

Question 17

Describe how different arrangements of collagen in different tissues give specific functions

Answer 17

Tendons: strands run parallel so provide tensile strength in one direction

Skin: cross over each other, providing more universal tensile strength

Question 18

What type of collagen is found in the basement membrane?

Answer 18

Type IV - dimers and tetramers form complex sheet network

Question 19

What do elastic fibres do, and how?

Answer 19

Give tissues elasticity e.g. Blood vessels, lungs and skin; collagen and elastic fibres often interwoven to limit the extent of stretching; consist of elastin core with microfibrils rich in fibrillin

Question 20

What do laminins do?

Answer 20

Have many NH2 groups to bind to other molecules in basement membrane
E.g. Integrins, dystroglycan, perlecan, nidogen

Question 21

What is the structure of Laminin?

Answer 21

Alpha, beta, gamma chains in crucifix shape. Coiled-coil domain in long bit

Question 22

What can congenital muscular dystrophy be caused by?

Answer 22

Absence of alpha2 chain in laminin 2.

Hypotonia, weakness, joint deformaties from birth

Question 23

Where are laminins found?

Answer 23

Basement membrane only

Question 24

Where are fibronectins found?

Answer 24

Connective tissue (not BM)

Question 25

What do fibronectins do?

Answer 25

Multi-adhesive. Can exist as soluble plasma proteins or insoluble fibrils in matrix.
Help promote blood clotting

Question 26

What are proteoglycans?

Answer 26

Glycoproteins composed of core protein with one or more glycosaminoglycan (GAG) chains - long, unbranched sugars consisting of repeating disaccharides; occupy large volume relative to mass - hydrated gels resistant to compression

Question 27

What does decorin do?

Answer 27

Regulate size of collagen fibres

Question 28

What is the structure of cartilage matrix?

Answer 28

Single T II Collagen fibril embedded in proteoglycan network

Question 29

What is aggrecan?

Answer 29

Major cartilage matrix constituent; forms aggregates with hyaluronan

Question 30

What is Hyaline cartilage?

Answer 30

Most abundant - rich in aggrecan, and cushions ends of long bones