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Intercal - Advanced molecules, membranes and cells > Cell-substrate interactions 1 > Flashcards

Cell-substrate interactions 1 Flashcards

1
Q

What is the extra cellular matrix

A

Collection of extracellular molecules that provides structural and biochemical support to the surrounding cells

It is DYNAMIC not static

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2
Q

What two parts form the ECM

A

Interstitial matrix
Basement membrane

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3
Q

Why is the ECM important

A

Needed for cell - migration, proliferation differentation, immune system and tissue repair

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4
Q

What makes up the ECM

A

Collagens
Elastins
Proteoglycans - hyaluronic acid
Glycoproteins - fibronectin and laminin

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5
Q

How many collagen genes are there and what do they code for

A

25 - alpha chains

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6
Q

What is the process of collagen assembly

A

Alpha-chain X3 –> Procollagen –> (CLEAVED) collagen fibril –> collagen fibre

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7
Q

Why is collagen important

A

Resist tensile forces

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8
Q

What is the role of type 1 collagen

A

Principle collagen of skin and bone and the commonest.

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9
Q

How does collagen form correctly to ensure it is the correct type

A

Requries integrins and other adhesion molecules.

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10
Q

How is the alpha chain triple-helix stabilised

A

Via hydroxyaltion of proline using vitamin C

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11
Q

How does scurvy affect collagen

A

Dont have vitamin C to stabilse these alpha helixes of the collagen

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12
Q

What are the features of type IV collagen

A

Flexible and assemble in sheet structure - make basal lamina

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13
Q

Why is collagen related to oestogenesis imperfecta

A

Type 1 collagen mutation that is autosomal dominant - weak bones and irregular connective tissue

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14
Q

Why is collagen related to ehlers-danlos syndrome

A

Weak and ruptured arteries caused by different types of mutations of collagen

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15
Q

Why is collagen related to alport syndrome

A

Mutations in collagen IV - mostly xlinked and have problems with sight, hearing and renal

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16
Q

Why is collagen related to knobloch syndrome

A

Autosomal recessive disorder which presents with myopia, cataracts, dislocated lens and retinal detachment

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17
Q

Why is collagen related to osteoporosis

A

Reduced density of collagen with age

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18
Q

What is the role of elastin

A

Gives elasticity to tissues

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19
Q

Why is eleastin interwoven with collagen

A

To limit stretching and prevent fibre tears

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20
Q

How is elastin formed

A

Tropoelastin and assembled into elastin fibres outside the cells in the plasma membrane. where they cross link and generate as sheets by lysine molecules.

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21
Q

What are proteoglycans

A

formed of glycosaminoglycans (GAGs) covalently attached to the core proteins.

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22
Q

What is the role of proteoglycans

A

Highly negative charge to attract positive cations to suck water into the matrix and provide a cushion

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23
Q

What are the 4 main types of proteoglycans

A

Hydroronic acis
Chondroitin sulfate
Heparan sulfate
Keratan sulfate

Differ depending on sugar

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24
Q

Where are proteoglycans important

A

Joints - hydronic acid

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25
Q

What is the role of glycoproteins

A

Mediate cell adhesion to matrix

26
Q

What is the structure of laminin

A

3 chains - alpha, beta, gamma

27
Q

How many genes if fibronectin is there

A

1 - alternative splicing makes different types of fibronectin

28
Q

What type of fibronectin is soluble

A

Plasma fibronectin - all others are insoluble

29
Q

Where is fibronectin mostly found

A

Surface of cells

30
Q

How does fibronectin work

A

Integrins bind to RGD domain on fibronectin which stretches them

31
Q

What are integrins

A

Large family of transmembrane proteins that function as the major receptors for cell adhesion via connecting intracellularly and extracellularly

32
Q

How many integrins form

A

24 based off of 18 alpha subunits and 8 beta subunits - the combination decide the substrate affinity

RNA splicing gives different integrins

33
Q

What are the main 4 collagen receptors

A

Collagen receptor
RGD receptor (fibronectin)
Laminin receptor
Leukocyte-specific receptor

34
Q

Why do non-attached cells not grow

A

Require integrins for growth factor binding.

35
Q

How are integrins activated

A

Talin binds intracellualrly which integrins undergo a conformational change to expose extracelluar binding part.

Go from bent to straight

36
Q

Give an example of integrin binding

A

Platelet aggregation

37
Q

How do integrins help cell migration

A

Looses affinity for site A and increases affinity for surface of site B which moves it towards B

38
Q

Give two integrin inhibitors

A

ICAP
Sharpin

39
Q

Give 3 integrin activatiors

A

Kindlins
Talin
KRIT1

40
Q

Why does fibronectin not self-assemble

A

Self-assembling domains not exposed so need some force to stretch it to expose them

41
Q

How does fibronectin assembly require

A

Actin - fibronectin binds to cell which causes intracellular signalling to form an actin cystoskeloton which stretches the cell and allows more fibronectin to binds

42
Q

What is the ECM linked to inside the cell

A

Actin cytoskeleton via fibronectin

43
Q

What causes muscular dystrophy

A

Defect in dystrophin which binds actin in muscle cells to fibronectin outside via integrins.

44
Q

Give the three areas of cell adhesion issues

A

Defects in matrix/assembly - scurvy, ehlers-danlos syndrome

Defects in ECM receptors - leukocyte adhesion deficency

Defects in cytoskeleton proteins - muscular dystrophy

45
Q

How can staph aureus cause cell adhesion issues

A

Has evolved a way to enter cells - binds to fibronectin which the fibronectin binds to integrin allowing the staph aureus to attach to the cells and change the cell shape to allow it to be englufed by the cell but stay alive, making it more resistant to antibiotics and stay hidden.

46
Q

What role does hyaluronic acid have in cancer

WIDER READING - Stern 2005

A

Higher levels of hyaluronic acid on cancer cells are indicators of a worse outcome.
Its receptor CD44, participates in cell adhesion interactions which are required by tumour cells.

47
Q

How has hyaluronic acid been used in cosmetics

WIDER READING - Gold 2007

A

As it can attract water, it is used as a dermal filler to hide wrinkles.

48
Q

Where is hyaluronic acid important in cell adhesion

WIDER READING - Litwiniuk, M; Krejner, A; Speyrer, MS; Gauto, AR; Grzela, T (2016)

A

Formation of granulation tissue as it produces a hydrated matrix to allow cell migration.
It forms links with protein kinases associated with cell movemement (extracellular signal-regulated kinase etc)

49
Q

Why is collagen so useful in bone grafts

WIDER READING - Cunniffee 2011

A

Cannot be broken down by enzymes due to its triple-helix structure, allowing cells to attach and form an effective ECM.

50
Q

What roles does collagen have in wound healing

WIDER READING - Rangaraj 2011

A

Guides fibroblasts to migrate in ECM
Haemostatic - cell adhesion of platelets to form haemostatic plug.
Benefits as a wound dressing due to antibacterial properties

51
Q

What is the pathogenesis of osteogenesis imperfecta

WIDER READING - Xiao 2011

A

Glycine substitute to alanine which is bigger, causes buldges in collagens triple helix structure which influenceses its interaction and binding and impairs them.

Multitude of other pathphysiologies but this is one of them

52
Q

How does osteogenesis imperfecta present

WIDER READING - LEE 2019

A

Hearing loss, breathing problems, blue sclerae, loose joints, dental issues, short stature

53
Q

What is the pathophysiology of alport syndrome

WIDER READING - Nozu 2019

A

Mutations in 3/6 collagen genes - COLD4A3, COL4A5, COL4A4

Important for the basement membrane in the kidney, inner ear and eye causing issues in these

54
Q

Give some ligands for integrins

A

Fibronectin
Vitronectin
Collagen
Laminin

55
Q

How do integrins help cells move

WIDER READING - Paul 2015

A

The ones at the front bind to the ECM whilst the ones at the back are endocytosed and moved to the front of the cell via the endocytic cycle where they are added to the front surface.

56
Q

What is the role of integrins in nerve repair

wider reading - Nieuwenhuis 2018

A

Present at the growth cone in damaged PNS neurons and promote axon regeneration

57
Q

How does laminin help in neural development

WIDER READING - Sarthy 1990

A

Lays down path for growth cones to follow of the retinal ganglion cells to get from the retina to the tectum.

58
Q

Is fibronectin important

WIDER READING - E L George 1993

A

Needed for embryogenesis as results in neural tube and vascular development defects when inactivate the fibronectin gene in mice.

(Mesodermal defects)

59
Q

What transmembrane protein is essential for fibronectin matrix formation

WIDER READING - Lugano 2018

A

CD93 - if knockedown then these cells result in a distruption of fibrillogenesis in both human blood endothelial cells and the retina

60
Q

Explain the pathophysiology of Ducheene’s muscular dystrophy and how that relates to

WIDER READING - Niggli 2008

A

Genetic mutation in dystrophin gene which is responsible for connecting actin cytoskeleton to the basal lamina within muscle fibres.

When dystrophin is absent, calcium accumulates which lies within the cell membrane which causes water to move into the cell due to signalling pathway changes and causes mitochondria to burst causing muscle cell death

Intercal - Advanced molecules, membranes and cells (31 decks)

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