Cell matrix signal Flashcards

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1
Q

extracellular matrix surround cells

A

chondrocytes - mesenchymal cell

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2
Q

cells sitting on matrix

A

epithelial, lining tube, skin

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3
Q

matrix

A

insoluble, amalgam of protein + proteoglycan = bed around cell
can be cell signalling molecules as well

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4
Q

dermis

A

below epithelial in skin

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5
Q

matrix function

A

for strength - tensile and compress - when pulled or pressed - returns back to original form

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6
Q

roles of matrix

A

integrate cells into tissue and limits it by setting boundaries
signal info to cells about surroundings

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7
Q

skin - dermis

A

loose connective tissue laid with many fibres

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8
Q

skin - dense connective tissue

A

laid - more defined regularly packed sheets

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9
Q

basement membrane

A

basal lamina between blood vessel, muscle, epithelium

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10
Q

basement membrane signalling function

A

migration - during development/ healing

cell survival and differentiation

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11
Q

basement membrane physical function

A

tissue border
strengthens
filter effect

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12
Q

basement membrane in ECM

A

structural protein
proteoglycan
cell adhesive protein

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13
Q

tensile strength by collagen

A

around 7 forms - act as fibrils/associated to fibrils or sheet

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14
Q

tensile strength characteristic

A

major structural protein and most abundant protein in body

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15
Q

collagen sequence

A

repeat of Gly-XY sequence 300-400 times

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16
Q

collagen helix

A

collagen sequence folds
LH helix than alpha
stable

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17
Q

trimeric collagen (TC)

A

3 helices wrap - RHS helix

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18
Q

RHS helix

A

right hand super helix

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19
Q

Gly-XY

A

XY - often lysine/ proline

modify to -OH form

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20
Q

fibrillar collagen

A

include collagen I, II, III

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21
Q

fibrillar collagen packing

A

loose connective - lots of collagen III

dense connective - more collagen 1 and 2

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22
Q

TC secreted

A

in ECM in regular array - places in off set array system

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23
Q

TC region

A

at high dense and less protein = bands in TEM and SEM

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24
Q

TEM/SEM

A

transmission/scanning e- micrograph

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25
Q

collagen formation

non-collagenous region (no GlyXY)

A

N and C terminal ends

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26
Q

collagenous repeat

A

at the centre

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27
Q

collagen formation

A

produced in ER and secreted

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28
Q

some XY

A

hydroxylated and other (selected hydroxylysines) - glycosylated

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29
Q

trimeric Shelix

A

3 chains (pro alpha chains) weaved at C-terminus to N which is then placed in secreted vacuole for secretion out of Golgi

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30
Q

shift base

A

used to form covalent linkage between trimeric collagen fibril

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31
Q

collagen formation on secretion

A

C and N terminal non-collagenous region is remove = mature collagen molecule - able to lay down in arrays into fibrils
cleaved by enzyme out of the cells

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32
Q

C and N terminal non-collagenous

A

prevent fibril forming inside cell

if removed inside cell - insoluble in Golgi and vacuole therefore kills the cell

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33
Q

collagen molecules characteristics

A

long half life

degraded/reformed at stress, healing, cell infiltration etc

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34
Q

mutation of enzyme used to cleave

A

can’t form fibrils

detect in collagen deposition therefore weakens it

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35
Q

MMP

A

matrix metalloproteinase

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36
Q

MMP function

A

released as they migrate through CT

regulate breakdown of collagenous matrix in its modelling

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37
Q

disease - ascorbic acid deficiency

A

scurvy - in absence collagen trimer and fibrils less stable - weaker
acid - cofactor for XY hydroxylase - for collagen crosslink

38
Q

elastin

A

fibres formed of polymer elastic

monomeric tropoelastin

39
Q

cross linkage

A

between elastin by hydroxy linkages

increase linkage over time

40
Q

returning to original of elastin

A

lacks defined structure

highly HP = random coil which returns back

41
Q

properties of elastin in tissues of

A

blood vessels
lungs
elastic cartilage

42
Q

synthesis of elastin

A

during foetus and childhood

but very limited in later life = wrinkles

43
Q

elastase

A

secreted by neutrophils
destroyed elastin replaced with collagen after fibres are broken down by inflammation
= fibrosis and scarring

44
Q

proteoglycan

A

give compressive strength by water retention

core has highly charged sugar attached and attract H2O and Na+ = hydrated porous gel

45
Q

hydrated porous gel

A

allow motion of nutrient and waste products about isolated cell
e.g. chondrocytes

46
Q

sugar and GAG

A

repeated sequence of disaccharides (tetrasaccharide link) and GAG sequence

47
Q

GAG sequence

A

glycosaminoglycan sequence

48
Q

proteoglycan function - resistant to compression

A

alter charge density on pressure

charged chains repel and water gel like

49
Q

proteoglycan function - highly charged

A

binding site for many molecules - GF(FGF) and cytokines (TGFb)
released on proteoglycan damage

50
Q

proteoglycan function coreceptor

A

inducer for GF

51
Q

cell adhesion molecule

A

fibronectin

laminin

52
Q

fibronectin

A

in loose connective tissue

disulphide linked - dimer

53
Q

6 domain in fibronectin

A
self association
collagen binding
cell binding
heparin binding
C-terminus
54
Q

function of 6 domain in fibronectin

A

interact with different ECM molecules

55
Q

C-terminus of 6 domain

A

small (RGD) and synergy region

56
Q

RGD

A

Arg, Gly, Asp

bind to integrin - fibronectin act as link to surface and matrix

57
Q

collagen binding and self-association - 6 domain

A

bind multiple fibronectin

58
Q

heparin binding region

A

within heparin sulphate

59
Q

cell binding of fibronectin via specific integrin receptor induces

A

remodelling of cytoskeleton
cell migration
proliferation

60
Q

remodelling of cytoskeleton

A

signal cell to attach

61
Q

cell migration

A

move - attach to surrounding - transport

62
Q

proliferation of integrin receptor

A

in healing as example

63
Q

laminin

A

a, b and y chain = trimer

64
Q

laminin - G-domain

A

bind to receptor and integrin receptor and other receptors

65
Q

sheet of laminin

A

trimer interacts in presence of Ca2+

66
Q

self assemble mesh

A

centre go down and bind to receptor on cell surface

interacting with proteoglycans, collagen and cell receptors

67
Q

basement membrane signals

A

migration, cell survival and differentiation

68
Q

losing receptor in mesh

A

cell has tendency to die

69
Q

integrin families matrix receptor

A

heterodimeric receptor - ab subunit separate

70
Q

matrix receptor has transmembrane region

A

bind to linker and attach to part of cytoskeleton

71
Q

specific integrin - function

A

bind to specific ECM components especially laminin and fibronectin

72
Q

integrin

A

nucleation site for actin polymerisation = stable contact between contractile machinery and ECM
linkage from cytoskeleton - in cell and matrix out of cell

73
Q

cell contract and movement

A

pull on actin filament and transfer force ECM

allow cell to generate traction

74
Q

traction of cells for movement

A

lamellipodia

filopodia

75
Q

lamellipodia (Lp)

A

push

large amounts of integrins

76
Q

filopodia (Fp)

A

spike

extension

77
Q

cell contraction and movement - migration

A

heals wounds

immune cell and metastasis (tumour)

78
Q

moving forwards - in terms of Lp and Fp

A

Fp interacts with matrix and convert to Lp to move

79
Q

focal adhesion

A

area of clustering
integrin binds to specific sequence on ECM
e.g. RGD receptor or more complex site

80
Q

roles of focal adhesion

A

anchor cells to ECM
migration
signal from ECM

81
Q

focal adhesion - actin filaments

A

comes in from cytosol and linker protein attach to integrin receptor - sits through membrane and binds to ECM

82
Q

linker proteins on actin filments

A

vinculin

alpha-actinin

83
Q

assembly of focal adhesion

A

has many fibre therefore huge cluster of integrins

84
Q

hemidesmosomes

A

specific integrin bind laminin in BM to intermediate filaments (keratin) via plectin

85
Q

BM

A

basement membrane

86
Q

desmosomes

A

similar to hemidesmosomes

only has keratin filaments

87
Q

difference between hemidesmosomes and desmosomes - function

A

act as interaction between keratin filaments between cells

while hemidesmosomes - intermediate filaments and BM

88
Q

defect in molecule producing hemidesmosome/receptor/laminin

A

weak attraction from ECM to BM
therefore when force added on cell - pull away
= Epidermolysis bullosa

89
Q

integrin clustering causes

with example

A

other signalling molecules bind to focal adhesion sites
concentrated at site
e.g. FAK - at high conc - function activate

90
Q

ECM attached to integrins pathways

A

actin organisation
cell spreading
cell motility
survival proliferation

91
Q

FAK

A

focal adhesion kinase