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Phase 1 > Extracellular Matrix > Flashcards

Extracellular Matrix Flashcards

1
Q

Define extracellular matrix (ECM):

A

The non-cellular component present within all tissues and organs
- Complex network of proteins and polysaccharides secreted by local cells and remains closely associated with these cells

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2
Q

What are the 2 main types of ECM?

A
  1. Interstitial connective tissue matrix: surrounding cells and providing structural scaffolding for tissues
  2. Basement membrane: separating the epithelium from the surrounding stroma
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3
Q

Function of ECM:

A

Overall: Provides structural, adhesive and biochemical signalling support
1. Provide mechanical and structural support
2. Tensile strength
3. Determines cellular environment: anchorage, embryonic development, pathways for cellular migration, growth factors, etc.

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4
Q

Where is it found?

A

Bones, tendons, cartilage, blood vessels, vitreous body of the eye, cornea, dermal layer of skin, basement membranes (basically everywhere!)

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5
Q

Two different groups of the acellular component of connective tissue (aka ECM)

A

Fibres and ground substance

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6
Q

What are the 5 classes of macromolecules found in ECM:

A

Collagens
Elastins
Proteoglycans
Hyaluronan (a glycosaminoglycan)
Other glycoproteins

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7
Q

Collagen: what is it? structure? function? types?

A

Major insoluble fibrous protien found in ECM
3 collagen polypeptides forming triple helix,
gly-X-Y repeat motif
Provides tensile strength
Can be fibrillar (provides strength) or sheet/ network forming (such as basement membrane, provides support or filtration)

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8
Q

Where is type I collagen found?

A

Dermis, tendons, ligaments, bones, fibrocartilage

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9
Q

Where is type II collagen found?

A

Hyaline cartilage

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10
Q

Where is type III collagen (reticulin) found?

A

Liver, bone marrow, lymphoid organs, granulation tissue

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11
Q

Where is type IV collagen found?

A

Basement membrane

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12
Q

Where is type V collagen found?

A

Linker to basement membrane, cornea (associated with collagen 1)

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13
Q

Elastin: what is it? structure? function?

A

Structural protein arranged as fibres
Assembled into functional fibres requiring the presence of a structural glycoprotein (fibrillin)
Allows stretch and recoil properties (lung, bladder, blood vessels)

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14
Q

What is ground susbtance?

A

The non fibrous molecules found in ECM
It is clear, gelatinous substance filling space between fibres and cells in connective tissue

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15
Q

What is ground substance made from? Function?

A

Large molecules: glycosaminoglycans (GAGs) which link together (with core protein) to form even larger molecules called proteoglycans
Function: attract water as very negatively charged making ground substance very good at absorbing water, provides resistance to compressive forces (water makes up 80% of ECM)

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16
Q

What are glycosaminoglycans? (aka, structure, function, 4 example and location)

A

AKA mucopolysaccharides
Structure: shcains of repeating disaccharide units, very hydrophilic, adopt extended confomation of water-swollen 3D network
Function: carbohydrate component of proteoglycans, attract water (cushioning and hydrating properties)
Examples:
- Hyaluronic acid (hyaluronan): synovial fluid
- Chondroitin sulphate: cartilage
- Keratan sulphate: cartilage
- Heparan sulphate: basement membrane

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17
Q

What are proteoglyclans? (aka, structure, function, examples and location)

A

AKA mucoproteins
Structure: protein core with GAGs attached (forming bottle brush structure), 90-95% GAG
Examples:
- Aggrecan: cartilage (hydrating properteis, interacts with collagen I for tensile strength)
- Perlecan: basement membrane
- Syndecan: cartilage
- Decorin: widespread in connective tissue

18
Q

Examples of other glycoproteins involved in ECM:

A

Fibrillin: controls deposition and orientation elastin
Fibronectin: linker role in BM, organises ECM and participates in cell attachment to BM
Laminin: primary organiser of basement membrane

19
Q

How is ECM synthesises?
Synthesis of collagen, elastin and proteoglycans

A

Local cells produce surrounding ECM (fibroblasts responsible for producing collagen in skin)
Production of collagen by fibroblast:
1. Secreted from fibroblasts as procollagen
2. Undergoes glycosylation and hydroxylation as posttranslational modification
3. Amino acids at end of procollagen fibres cleaved off outside cell to form collagen
4. Collagen aggregates into fibres and assembles into triple helix
Production of Elastin (II):
1. Secreted from cell as tropoelastin
2. Undergoes hydroxylation
2. Assembled into fibres with the addition on fibrillin which crosslinks fibres together
Production of Proteoglycans:
- Core protein made on rER
- Addition of carborbohydrates in Golgi
- Delivered to ECM by exocytosis
- Assembles with other ECM components

20
Q

How is ECM degraded?

A

Not a static structure: constant deposition, degradation and modification
- Collegenases breakdown ECM
- Matrix-metalloporteinases (MMPs) break down basement membrane

21
Q

What can occur when deregulated ECM remodelling occurs?

A

Hyperproliferation of fibroblast can cause excess ECM production.
Release of collangenase from pathogens can allow invasion of host by bacteria
Excessive activation of MMPs can allow tumour cell invasion/ metastisis

22
Q

ECM in basement membrane: components, structure, location, function

A

Basement membrane:
- Collagen IV, nidogen, perlecan, laminin
- Thin tough sheet of ECM in a mat-like arrangement
- Found underneath (epithelia, endothelia) and arround cells (myocytes, neurons, adipocytes, kidney glomerulus)
- Provides structure, support, binds to underlying connective tissue, mediates signals between cell, determines cell polarity, permeability, cell migration, barrier to downward growth

23
Q

Disorder of basement membrane (4 examples and reasons)

A

Cancer - epithelial tumours regarded as malignant once BM is breached
Dibaetes mellitus - thickening of BM in glomerulus changes permeability
Epidermolysis bullosa - attachment of epidermis to basement membrane damaged
Goodpastures syndrome - autoantibodies to collagen IV destroy BM in glomerulus and lung

24
Q

Where can specialised connective tissue be found?

A

Bone, cartilage, adipose tissue, blood, bone marrow, lymphoid tissue

25
Q

Composition of ECM in bone

A

Contains cellular and acellular components
Cellular: osteoblasts, osteoclasts, osteocytes
Acellular: organic osteoid material (30%) made frm type I collagen and osteocalcin, inorganic (70%) composed of hydroxyapatite

26
Q

Composition of cartilage

A
  • Synthesised by chondrocytes
  • Less rigid than bone
    Formed from:
  • Type II collagen
  • Chondroitin sulphate
  • Ketaran sulphate
  • Hyaluronic acid
  • Aggrecan (large assembly of proteoglycans)
  • 80% water
27
Q

3 types of cartilage: features, location

A

Hyaline:
- few visible collagen fibres, avascular, perichondium (fibrous layer surounding tissue and extending into tissue)
- Nasal septum, larynx, tracheal rings, articular surfaces, etc
Fibrocartilage:
- abundant collagen fibres, avascular, no perichondrium
- IVD, sternoclavicular joint, pubic symphysis
Elastic cartilgae:
- elastic fibres, avascular, perichodrium
- external ear, epiglottis, auditory tube

28
Q

Exampls of medical conditions associated with defects in ECM:

A

Osteoarthris: over-degredation of ECM in hyaline cartilage
Fibrosis: overproduction of ECM
Supravalvular Aortic Stenosis: arterial defects caused by mutations in elastin, section of aorta narrowed, can’t accomidate blood from heart
Marfan sydrome: mutation in fibrillin gene, affects connective tissue of skin, bone, blood vessels, other organs, vision problems, heart defects, long slender limbs, finger and toes
Alport syndrome: mutations in collagen IV gene, BM in glomerulus of kidney abnormalities, loss of kideny fuction
Elhers-Danlos syndrome: mutation in collagen gene and others, affects connective tissue of skin, bone, blood vessels and other organs, causes hypermobility and stretchy, fragile skin

29
Q

Where is the GAG hyaluronic acid (hyaluronan) found?

A

Synovial fluid

30
Q

Where is the GAG chondroitin sulphate found?

A

cartilage

31
Q

Where is the GAG keratan sulfate found?

A

cartilage

32
Q

Where is the GAG heparan sulphate found?

A

basement membrane

33
Q

What GAGs form aggrecan? Where is it found?

A

Chondroitin sulphate
Keratan sulphate

Cartilage

34
Q

What GAG forms perlecan? Where is it found?

A

heparan sulphate

BM

35
Q

What GAGs form syndecan? Where is it found?

A

chondroitin sulphate
heparan sulphate

cartilage

36
Q

What GAGs form decorin? Where is it found?

A

Chondroitin sulphate
dermatan sulphate

Widespread in connective tissues

37
Q

What results from the dysfunction of elastin?

A

Supreavalvular aortic stenosis (SVAS) - arterial defects

38
Q

What results from the dysfunction of fibrillin-1?

A

Marfan Syndrome: skeletal, ocular and cardiovascular abnormalities

39
Q

What results from the dysfunction of collagen 1?

A

Ehlers-Danlos Syndrome: joint and skin abnormalities

40
Q

What results from the dysfunction of collagen IV?

A

Alport syndrome - chronic kidney disease
Goodpastures’s disease - glomerulonepritis and pulmonary haemorrhage

Phase 1 (30 decks)

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