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POM Y1 Imperial > Extracellular matrix > Flashcards

Extracellular matrix Flashcards

1
Q

What are the two types of components of the ECM?

A

Fibrillar and non-frbillar

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2
Q

What is the function of the ECM?

A

Architectural (Mechanical stability)
Instructional (Influences cell behaviour)
Physical support, mechanical and physicochemical properties of tissue: Influences growth, adhesion, differentiation, and status of cells

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3
Q

What molecules do connective tissue comprise of?

A

Proteoglycans
Collagen
Glycoproteins (Multi-adhesive)

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4
Q

Which Collagen molecules are fibrillar?

A

Type 1-3

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5
Q

Which collagen forms the basement membrane?

A

Type 4

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6
Q

Name 2 multi-adhesive glycoproteins?

A

Laminins

Fibronectin

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7
Q

Name 4 proteoglycans?

A

Aggrecan, Versican, Decorin, Perlecan

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8
Q

Why can collagen form a tight-compact helical structure?

A

Glycine-x-y repeat has a single variable group consisting of a hydrogen ion, therefore spatially occupying minimal space

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9
Q

What is the secondary structure of collagen?

A

Involves hydrogen bonding which occur between the amino and carboxyl groups of the amino acid to form the left handed helix

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10
Q

What is the quaternary structure of collagen?

A

3 polypeptide helices (Homotrimer) bond together to form a right handed triple helix, helical structure is maintained through hydrogen bonding
Crosslinking bridges

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11
Q

How do collagen fibrils form?

A

Covalent bonding between multiple triple helices

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12
Q

What are the structural properties of collagen?

A

They provide high tensile strength and flexibility

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13
Q

Name the genetic disease attributed to dysfunctional triple helix collagen:

A

Osteogenesis imperfecta

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14
Q

Is collagen 1 a heterotrimer or homotrimer?

A

Heterotrimer
2- alpha 1
alpha 2(1)

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15
Q

What type of trimers are collagens 2 &3?

A

Homotrimers

alpha-1-2) and alpha (1-3

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16
Q

What contributes towards interchain hydrogen bonding within collagen molecules?

A

The hydroxylation of proline via post-translational modification (Holds the triple helix)
Hydroxyproline

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17
Q

What is the purpose of lysine and hydroxylysine?

A

Formation of covalent cross-linkages between collagen molecules

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18
Q

What is the pathophysiology of scurvy?

A

Vitamin C deficiency
Vitamin C is a cofactor for the hydroxylation of proline and lysine (Prolyl hydroxylase and lysyl hydroxylase)
Underhydroxyalted collagens result in a reduction of tissue stability

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19
Q

Where are collagen pro-alpha chains formed?

A

Ribosomes

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20
Q

What is Ehlers-Danlos Syndrome (EDS)?

A

Inherited connective tissue disorder
Symptoms: Stretchy skin, and loose joints
Mutations in collagen, reducing collagen structure, and processing

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21
Q

What two fibres do basement membranes comprise of?

A

Mucopolysaccharides and protein fibres

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22
Q

What is alport syndrome?

A

Mutations in collagen IV (COL4A3, COL4A4, COL4A5 genes)

Laminated glomerular basement membrane, associated with progressive kidney function loss, and hearing impairment

23
Q

What protein comprises elastic fibres?

A

Elastin and fibrillin

24
Q

What is fibrillin?

A

Glycoprotein secreted into the extracellular matrix by fibroblasts, fixated with microfibrils to provide scaffold for elastin deposition

25
Q

What is Marfan’s syndrome?

A

Mutations in fibrillin-1 affect skeletal occular and cardiovascular systems
Results in elevated levels of transforming growth factor beta- degrades elastic fibres

26
Q

What are patients with Marfan’s syndrome susceptible to?

A

Aortic ruptures

Manifestations include arachnodactyly

27
Q

What two amino-acids are prevalent in elastin?

A

Alanine and lysine

28
Q

What is the structure of laminins?

A

Heterotrimeric proteins consisting of alpha, beta and gamma chains

29
Q

What type of shape do the chains make for laminins?

A

Cross-shape

30
Q

What type of protein are laminins?

A

Multi-adhesive glycoproteins

31
Q

What do laminins interact with?

A

Integrins and dystroglycan (cell-surface receptors), self associated with basement membrane

32
Q

What laminin chain is absent within congenital muscular dystrophy?

A

Alpha chain

33
Q

What are the symptoms fo muscular dystrophy and epidermolysis bullosa?

A

Hypotonia (decrease in muscular tone)
Join deformations
generalised weakness

34
Q

What are fibronectins?

A

Multi-adhesive glycoproteins existing as an insoluble fibrillar matrix or as a soluble plasma protein
Form dimers

35
Q

What are the functions of fibronectins?

A

Regulate cell adhesion and migration
Embyrogenesis and tissue repair
Promotes blood clotting, and forms a mechanical continuum with actin cytoskeleton

36
Q

What are proteoglycans?

A

Core proteins

37
Q

What chains are proteoglycan core proteins covalently attached to?

A

Glycosaminoglycan (GAG)

38
Q

What are the basement membrane proteoglycans?

A

Perlecan

39
Q

Which proteoglycans are aggregating?

A

Aggrecan

40
Q

Which molecules do aggrecan interact with?

A

Hyaluronan

41
Q

Which molecule is decorin rich with?

A

Leucine

42
Q

What proteoglycan property do syndecans 1-4 exhibit?

A

Cell-surface

43
Q

What is the structure of GAG chains?

A

Repeating disaccharide units (Amino sugar, sulfated or carboxyalted); therefore exhibiting a negative charge

44
Q

Why is the exhibition of a high negative charge useful in GAG chains?

A

Attracts large cloud of cations, including Na+, thus enabling the extra-cellular matrix retaining large amounts of water (increase solute concentration promotes osmosis)

45
Q

What are the four groups of glycosaminoglycan?

A

Hyaluronan
Chondroitin Sulphate
Dermatan sulphate
Keratan sulphate

46
Q

What are the functional properties of hyaluronan?

A

High viscosity, plates role in lubrication of cartilaginous joint surfaces
Aids in repair process by mediating cell adhesion, diffentiation, motility and proliferation
Controls tissue hydration by retaining large amounts of water

47
Q

Why can hyaluronan store large quantities of water?

A

Coiled structure molecule results in large hydrophillic domains that bind to water through hydrogen bonding, releases water by compression

48
Q

How is hyaluronan distinctly synthesised?

A

Plasma membrane enzyme

It is unsulphated

49
Q

What is the benefit of highly sulphated aggrecan?

A

High negative charge, attracts cations, stores large quanities of water, compressive load, water is released
Aggrecan resists compressive forces

50
Q

What is osteoarthritis?

A

Erosive disease resulting in excessive extracellular matrix degradation.
Lubrication and protective properties of cartilage are reduced

51
Q

Which proteoglycan is cleaved in osteoarthritis?

A

Aggrecan is cleaved by aggrecanses and metalloproteinases, results in loss of synovium

52
Q

How is a the term used to describe the excessive production of fibrous connective tissue?

A

Fibrotic disorders

53
Q

Which cells are responsible for collagen synthesis?

A

Myofibroblasts

POM Y1 Imperial (34 decks)

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