Extracellular matrix Flashcards

1
Q

Specialised extracellular matrix

A

The ECM is point where cell makes contact for cell movement
Body made of aprox. 50% cells
Examples of specialised:
- Tendons - tensile strength allows muscles to move
- Bones - calcified
- Hair - Fibrous and loose
- Skin - Elastic (has elastin and collagen in)
- Cornea - transparent (no nucleus so eye can be functional)

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2
Q

ECM features

A

Extracellular meshwork of proteins and hydrated macromolecules
Regulates:
- Migration
- Tissue integrity and cell shape
- Proliferation (if not controlled get cancer)
- Differentiation

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3
Q

ECM appearance

A

Really need to look at the diagram

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4
Q

ECM types

A

Fibrous proteins:
- Provide strength
- Collagens
- Elastin
Adhesion proteins:
- Fibronectin
- Laminin
Hydrated macromolecules
- Glycosaminoglycans (Gags)
- Proteoglycans (Proteins + Gags)
Main ECM components
- Bacteria
- Air pockets
- Collagen
- Precipitate

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5
Q

Collagens

A

Are long strand, hold nucleus in position cell wants it
20-40 variants
Glycine-proline(y)-hydroxyproline(x) triplet repeats
Triple helix
3 alpha chains
Produced by fibroblasts and epithelia cells

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6
Q

Collagen defects

A

Ehlers-Danlos syndrome
Loses integrity of skin so it’s stretchy and can take it off
Vascular form - quite dangerous as it means heart is susceptible to lots of damage like arterial rupture

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7
Q

Collagen synthesis (need to go back over)

A

Synthesis is self deficient
Failure in the chains
Look at diagram

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8
Q

Elastin

A

Can adopt structure as it is being deformed, allows it to have finite limit so after that point it can’t stretch anymore
This allows it to keep some strength
Tropoelastin -> Elastin with help Lysyl Oxidase
is 50% of dry weight in aorta

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9
Q

Fibrillin

A

Elastin laid down over microfibril scaffold of fibrillin
Possible defect in it leads to marfan syndrome
Leads to uncontrolled growth, arm span longer than height, problems in joints and eyes
Can lead to aortic rupture due to being too much elastin and fibrin in aorta

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10
Q

GAG’s glycosaminoglycans

A

Disaccharide chains, 70-200 units long
Highly charged, makes them very sticky and can hold lot of water
Link tetrasaccharide is always conserved to link to GAG

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11
Q

Hyaluronan complexes - hyaluronic acid

A

Aggrecan is proteoglycan, bound to hyaluronan backbone by linking proteins, very good at holding water, important for water storage
Look at the diagram of it

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12
Q

Adhesion glycoproteins - laminin

A

Basal lamina determines polarisation of epithelium
Dense and supports epithelial cells
Hass ability to self assemble, has 3 chains, is bonding site for nitrogen, receptor for integrin

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13
Q

Adhesion glycoproteins - fibronectin (go back over)

A

There’s lots of charge in RGD sequence

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14
Q

Integrins (go back over)

A

Bind matrix through divalent cations
Removal cations cause cells to detach
Look at diagram

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15
Q

Focal adhesion

A

Where see contact between integrins and extracellular matrix
There is a protein that goes through membrane that helps binding occur on both sides

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16
Q

Focal adhesion components

A

Transmembrane receptor
Connection to cytoskeleton
Signalling

17
Q

Knockouts of focal adhesion proteins

A

β1-integrin
- Embryonic lethal at implantation (Day 5)
α5-integrin
- α5β1-integrin fibronectin receptor
- Embryonic lethal mesoderm development (Day 10)
Fibronectin
- Embryonic lethal (Day 9)
Talin
- Embryonic lethal (Day 6-8)

18
Q

Integrin related defects

A

αIIbβ3-integrin
- Platelets bind fibrinogen to clot blood
- Glanzmann’s thrombasthenia
- Bleeding gums and nose bleeds
β2-integrin
- Leukocyte Adhesion Deficiency (LAD) syndrome
- Impaired expression
- Recurrent bacterial infections

19
Q

Summary

A

Fibrous proteins (collagen + elastin) provide structural integrity
Matrix defects are common, result in diseases involving loss of tissue integrity
Sugars fill space
Adhesive matrix stimulates cells
Cell migration
Cell polarity