Extracellular Matrix

Question 1

What is the ECM?

Answer 1

Non-cellular compinent present within all tissues and organs

Question 2

What are the types of ECM?

Answer 2

• Interstitial Connective Tissue Matrix; surrounds cells and provides structural scaffolding for tissues
• Basement membrane; seperates epithelium from surrounding stroma

Question 3

Where may ECM be found?

Answer 3

• Bone
• Tendon
• Cartilage
• Cornea
• Blood vessel walls
• Dermal layer of skin
• Vitreous body of eye

-Basement Mmebrane

Question 4

What are the functions of the ECM (insterstitial connective tissue matrix)?

Answer 4

• Provides mechanical and structural support
• Tensile strength
• Determines cellular microenvironment;
• anchors cells through cell-ECM junctions
• strongly influences embryonic development
• provides pathway for cellular migration
• establishes and maintains stem cell niches

Question 5

What are the components of Interstitial connective tissue ECM?

Answer 5

Fibres- Collagen, Elastin
Ground Substance-
Proteoglycans, glycosaminoglycans, glycoproteins

Question 6

What is the structure of collagen?

Answer 6

3 collagen polypeptides form a triple helix

Question 7

What stain can be used to see elastin?

Answer 7

Van giesen stain

Question 8

What does assembly of elastin into functional fibres require?

Answer 8

Presence of glycoprotein-fibrillin.

Question 9

How is ECM arranged in connective tissue?

Answer 9

Can differ:
-Loose irregular connective tissue- lymphoid tissue
-Dense irregular connective tissue- dermis
OR SPECIALISED
-dense regular (tendons and ligaments)
-bone
-cartilage

Question 10

How are ECM fibres synthesised?

Answer 10

Collagen is synthesised as procollagen and post translational modifications glycosylation and hydroxylation form collagen.
Elastin is synthesised as tropelastin and post translation modification hydroxylation forms elastin.

Question 11

How are proteoglycans synthesised?

Answer 11

Core protein synthesised on rER.
Addition of polysaccharide as disaccharide repeats in golgi.
Delivered to extracellular compartment by exocytosis.
Assembly with other ECM components.

Question 12

What is ground substance?

Answer 12

• An amorphous, colourless, gelatinous material.
• Fills the spaces between fibres and cells.
• Consists of large molecules called glycosaminoglycans which link with a core protein to form proteoglycans.
• Very good at absorbing water, allowing it to be resistant to compressive forces.

Question 13

What are glycosaminoglycans (GAG’s)?

Answer 13

• Chains of repeating disaccharide units
• Extremely hydrophillic
• Enables matrices to withstand high compressive forces.

Question 14

What are examples of GAG’s in cartilage?

Answer 14

• Chondroitin sulfate

- Keratan sulfate

Question 15

What is basement membrane ECM composed of?

Answer 15

Composed of:

• collagen IV
• laminin
• nidogen
• perlecan

Question 16

What are some of the features of basement membrane ECM?

Answer 16

• A thin, tough sheet of ECM
• Mat like arrangement
• Can surround cells
• Can separate 2 sheets of cells eg. glomerulus in kidney

Question 17

What are the functions of basement membrane ECM?

Answer 17

• Support
• Path for cell migration
• Barrier to downward growth
• Permits flow of nutrients
• determines cell polarity
• binding to underlying connective tissue
• mediates signals between cells and connective tissue

Question 18

What are proteoglycans?

Answer 18

-Is a protein core + GAG’s

Question 19

What are examples of proteoglycans in the cartilage?

Answer 19

• Aggrecan; GAG’s: -keratan sulfate, chondroitin sulfate

- Syndecan; GAG’s:-chondroitin sulfate, heparan sulfate

Question 20

What are the other structural glycoproteins involved in ECM ground substance?

Answer 20

• Fibrillin; controls deposition and orientation of elastin
• Fibroconectin; linker role in basement membrane, organises ECM and participates in cell attatchment to BM.
• Laminin; Primary organiser of BM layer

Question 21

What are some disorders involved in the basement membrane?

Answer 21

• Cancer= epithelial tumours regarded as malignant once BM is breached
• Diabetes Mellitus= Thickening of BM in glomerulus changes permeability.
• Epidermis Bullosa= attatchment of epidermis to BM
• Goodpastures syndrome= Autoantibodies to collagen IV destroy BM in lung and glomerulus.

Question 22

How is the ECM in bone arranged?

Answer 22

The bone has an acellular and cellular part.
Acellular=ECM
Acellular part has organic and inorganic parts.
Inorganic part is hydroxyapatite (calcium salts)
Organic part is type 1 collagen and osteocalcin

Question 23

What is the cellular part of bone?

Answer 23

• Osteoblasts; synthesise osteoid
• Osteoclasts; degrade osteoid
• Osteocyte; used for maintenance

Question 24

What are the types of cartilage?

Answer 24

• Hyaline
• Articular
• Elastic
• Fibrocartilage

Question 25

What is cartilage synthesised by?

Answer 25

By chondrocytes

Question 26

What are some molecules that are in cartilage?

Answer 26

• Type II collagen
• Chondroitin sulfate
• Keratan sulfate
• hyaluronic acid+aggrecan to help attract H2O

Question 27

What can happen when the ECM goes wrong?

Answer 27

• Over degradation could lead to osteoarthritis

- Over production could lead to fibrosis

Question 28

What are specific conditions that could occur as a result of defected components in ECM?

Answer 28

• Elastin; Supraclavicular Aortic Stenosis
• Fibrillin 1; Marfan Syndrome
• Collagen 1; Ehlers-Danlos Syndrome
• Collagen IV; Alports Syndrome

Question 29

What are the consequences of deregulated ECM remodelling?

Answer 29

• ECM synthesis; hyperproliferation of fibroblasts; excess ECM, can lead to Fibrosis, Embryogenesis, Angiogenesis
• Pathogens may secrete collagenase and allow invasion of host by bacteria
• Excess activation can mean MMP’s are made and allow tumour cell invasion