extracellular matrix

Question 1

what is the ECM?

Answer 1

a complex network of proteins and carbohydrates filling spaces between cells
comprises of both fibrillar and non fibrillar components

Question 2

what are the ECM key functions?

Answer 2

physical support
determines mechanical and physiochemical properties of the tissue
influences the growth, adhesion and differentiation status of the cells and tissues with which it interacts
essential for development, tissue function and organogenesis

Question 3

what are the components of connective tissue?

Answer 3

collagens
type I-III(fibrillar)
type IV(basement membrane)

multi-adhesive glycoproteins
fibronectin, fibrinogen
laminins(basement membrane)

proteoglycans
aggrecan, versican, decorin
perlecan(basement membrane)

Question 4

what are the collagens in connective tissue?

Answer 4

type I-III(fibrillar)
type IV(basement membrane)

Question 5

what are the multi-adhesive glycoproteins in connective tissue?

Answer 5

fibronectin, fibrinogen

laminins(basement membrane)

Question 6

what are the proteoglycans in connective tissue?

Answer 6

aggrecan, versican, decorin

perlecan(basement membrane)

Question 7

what are the properties of tendon and skin?

Answer 7

tough and flexible

Question 8

what are the properties of bone?

Answer 8

hard and dense

Question 9

what are the properties of cartilage?

Answer 9

resilient and shock absorbing

Question 10

what is osteogenesis imperfecta caused by?

Answer 10

type I collagen mutation

Question 11

what is marfan’s syndrome caused by?

Answer 11

fibrillin 1 mutation

Question 12

what is alport’s syndrome caused by?

Answer 12

type IV collagen mutation

Question 13

what is epidermolysis bullosa caused by?

Answer 13

laminin 5 mutation in all 3 chains

Question 14

what is congenital muscular dystrophy caused by?

Answer 14

laminin 2 mutation

Question 15

what is hurler’s syndrome caused by?

Answer 15

alpha-L-iduronidase (enzyme used to degrabe glycosaminoglycns)

Question 16

what are some fibrotic disorders due to excessive ECM deposition?

Answer 16

liver fibrosis-cirrhosis
kidney fibrosis- diabetic nephropathy
lung fibrosis- idiopathic pulmonary fibrosis(IPF)

Question 17

what is osteoarthritis caused by?

Answer 17

loss of ECM

Question 18

what is type I collagen’s composition?

Answer 18

[alpha1(I)]2 [alpha2(I)]

Question 19

what is type II collagens composition?

Answer 19

[alpha1(II)]3

Question 20

what is type III collagens composition?

Answer 20

[alpha1(III)]3

Question 21

outline the collagen triple helix

Answer 21

gly-x-y repeat in each chain (glycine has small side chain so can fit in gaps)
fibrillar collagen chains form a left handed helix
three chains form a triple helix

Question 22

outline the makeup of collagen fibres

Answer 22

single collagen polypeptide chain

Question 23

outline collagen biosynthesis

Answer 23

procollagen (with non-collagenous domains at N and C termini)—-> domains removed for fibrillar collagens but remain for most of the rest—-> collagen forms fibrils—-> fibrils cross link to form fibres

Question 24

what causes the covalent cross link between collagen?

Answer 24

lysine and hydroxy-lysine involved

type and extent is tissue specific and changes with age

Question 25

what do prolyl and lysyl hydroxylases require?

Answer 25

Fe2+ and vitamin C

Question 26

what is scurvy caused by?

Answer 26

vitamin C deficiency resulting in under hydroxylated collagens reducing stability for tissue

Question 27

what are ehlers-danlos syndromes?

Answer 27

group of inherited connective tissue disorders | symptoms include loose joints and stretchy skin

Question 28

what do collagen types IX and XII do?

Answer 28

do NOT form fibrils but associate with fibrillar collagens and regulate the organisation of the collagen fibrils

Question 29

what does type IV collagen do?

Answer 29

network forming present in all basement membranes

Question 30

outline collagen type IV assembly

Answer 30

monomer(single strand)------>dimer(2 strands)----->tetramer(3 strands)----->supramolecular aggregate( many strands)

Question 31

what are basement membranes (basal laminae)

Answer 31

flexible thin mats of ECM underlying epithelial sheets and tubes highly specialised containing a distinct repertoire of collagens, glycoproteins and proteoglycans

Question 32

what do basal laminae surround?

Answer 32

muscle, peripheral nerve, fat cells and underlie most epithelia

Question 33

what does the glomerular basement membrane do(GBM)?

Answer 33

in the kidney it forms a key part of the filtration unit

Question 34

where are elastic fibres found ?

Answer 34

elastic tissues | skin, blood vessels and lungs

Question 35

what are elastic fibres made from?

Answer 35

an elastin protein core and microfibrils which are rich in fibrillin

Question 36

outline symptoms of marfan's syndrome

Answer 36

skeletal, ocular and cardiovascular systems primarily affected predisposed to aortic ruptures arachnodactyly (spider like fingers)

Question 37

outline the structure of elastin

Answer 37

two types of segments that alternate (hydrophobic regions and alpha-helical regions) with cross linked side chains

Question 38

outline what modular architecture means

Answer 38

proteins composed of characteristic domains of 50-200 amino acids this is what allows them to be multi-purpose

Question 39

outline the structure of laminins

Answer 39

heterotrimeric proteins alpha, beta and gamma chain form a cross shaped molecule very large

Question 40

what can laminins do?

Answer 40

``` multi adhesive ( integrins and dystroglycan) can self associate or interact with components such as type IV collagen, nidogen and proteoglycans ```

Question 41

how can fibronectins exist?

Answer 41

insoluble fibrillar matrix or soluble plasma protein

Question 42

what can fibronectins do?

Answer 42

multi adhesive interact with cell surface receptors and other matrix molecules regulate adhesion and migration wound healing

Question 43

what are proteoglycans?

Answer 43

core proteins that are covalently attached to glycosaminoglycan chains

Question 44

what are glycosaminoglycans(GAGs) made from?

Answer 44

repeating disaccharide units one sugar in each disaccharide being an amino sugars usually GAGs are sulphated or carboxylated (negative charge)

Question 45

what doe the negative charge of GAGs cause?

Answer 45

Na+ to be attracted which draws water into the ECM

Question 46

what are the families of proteoglycans? (4)

Answer 46

basement membrane proteoglycans aggregating proteoglycans small leucine-rich proteoglycans cell surface proteoglycans

Question 47

what is perlecan?

Answer 47

a basement membrane proteoglycan

Question 48

what is aggrecan?

Answer 48

an aggregating proteoglycan( interacts with hyaluronan)

Question 49

what is decorin?

Answer 49

a small leucine-rich proteoglycan

Question 50

what are syndecans 1-4?

Answer 50

cell surface proteoglycans

Question 51

what gives cartilage good tensile strength?

Answer 51

has a matrix rich in collagen with large amounts of GAGs in the meshwork

Question 52

what are the GAG chain groups?(4)

Answer 52

hyaluronan chondroitin sulphate and dermatan sulphate heparan sulphate keratan sulphate

Question 53

how is hyaluronan made?

Answer 53

spun out directly from an enzyme embedded in the plasma membrane

Question 54

what monomers make up hyaluronan?

Answer 54

glucuronic acid and N-acetylglucosamine

Question 55

what happens to the GAGs in aggrecan?

Answer 55

they are highly sulphated

Question 56

why are cations attracted to aggrecan?

Answer 56

because of the sulphated GAGs and the carboxyl groups

Question 57

what happens when aggrecan is compressed?

Answer 57

water is given up but regained when load is reduced

Question 58

outline osteoarthritis

Answer 58

results from excessive ECM degradation cushioning properties at end of cartilage is lost loss of aggrecan

Question 59

what happens when excess fibrous connective tissue is produced?

Answer 59

fibrotic diseases | damages structures