Extracellular Matrix

Question 1

what is the ECM?

Answer 1

non-cellular component present within all tissues and organs

Question 2

what are the 2 main types of ECM?

Answer 2

interstitial CT matrix - surrounds cells and provides structural scaffolding for tissues
basement membrane - separates epithelium from surrounding stroma

Question 3

what is the composition and function of ECM?

Answer 3

complex network of proteins and polysaccharides
provices structure, adhesive and biochemical signalling support

Question 4

where is ECM found?

Answer 4

bone, tendons, cartilage, blood vessel walls, vitreous body of the eye, cornea, dermal skin layer,

Question 5

what are the 3 classifications of ECM function?

Answer 5

provides mechanical/structural support
tensile strength
determines cellular microenvironment

Question 6

what is interstitial CT made of?

Answer 6

fibrous proteins (collagen/elastin)
ground substance (proteoglycans, glycosaminoglycans, glycoproteins)

Question 7

describe the structure of collagen in ECM

Answer 7

insoluble fibrous protein, 3 collagen polypeptides form a triple helix, Gly-X-Y repeat modifications occur

fibrillar (type 1/2) in skin, tendon and bone provide strength
sheet/network forming (type 4) in BM provides support/filtering

Question 8

explain the structure of elastin in ECM

Answer 8

fibrous structural protein
abundant in tissues requiring stretch and recoil properties
assemply into functional fibres requires presence of structural glycoprotein fibrillin

Question 9

describe ECM arrangement in CT

Answer 9

loose irregular CT - lymphoid tissue
dense irregular CT - dermis
specialised - dense regular (tendons/ligaments), bone, cartilage

Question 10

describe ground substsance

Answer 10

amorphous, gel-like, non-fibrous substance surrounding cells

Question 11

describe glycosaminoglycan structure

Answer 11

chains of repeating disaccharide units, carb components of proteoglycans
attracts water giving it gel/cushioning and hydrating properties
very hydrophilic

Question 12

describe proteoglycan structure

Answer 12

protein core + GAGs = ‘bottle-brush’ structure
90-95% carbs (GAG)

Question 13

give 3 examples of glycoproteins in ECM and their function

Answer 13

fibrillin - controls deposition/orientation of elastin
fibronectin - linker role in BM; organises ECM and participates in BM cell attachment
laminin - primary organiser in BM layer

Question 14

explain the synthesis, PTMs and protein assembly of ECM fibrous proteins

Answer 14

collagen - synthesised as procollagen, PTM either glycosylation or hydroxylation, protein assembled in triple helix

elastin - synthesised as tropoelastin, PTM hydroxylation, protein assembled in fibrillin scaffolded cross linked fibres

Question 15

explain the synthesis of ECM proteoglycans

Answer 15

synthesised on rER, addition of polysaccharide as disaccharide repeats in golgi, delivered to extracellular compartment by exocytosis, assembly with other ECM components

Question 16

describe ECM remodelling

Answer 16

deposition -> degredation -> modification
(reversible)

Question 17

give an example of deregulated ECM remodelling

Answer 17

excess activation of MMPs can cause a tumour cell invasion

Question 18

explain ECM structure in epithelial tissue

Answer 18

the BM
thin, tough, sheet of ECM with a mat-like arrangement

Question 19

describe the 3 ways BM can act on cells

Answer 19

lies underneath cells (epithelial/endothelial cells)
surrounds cells (muscle fibres)
separate 2 sheaths of cells (kidney and glomerulus)

Question 20

what are the functions of BM?

Answer 20

support, binds to underlying CT, mediates signals between cells and CT, determines cell polarity, permits nutrient flow, cell migration path, downward growth barrier

Question 21

give an example of a BM disorder

Answer 21

cancer - once BM is breached, epithelial tumours regarded as malignant

Question 22

describe the ECM in bone

Answer 22

organic (30%) -> type 1 collagen (osteocalcin)
inorganic (70%) -> hydroxyapatite
ECM in bone - osteoid

Question 23

name the 3 functional cell types in bone

Answer 23

osteoblast - matrix production
osteoclast - matrix resorption
osteocyte - maintenance

Question 24

what does cartilage contain to become a proteoglycan?

Answer 24

aggrecan + hyalraunic acid

Question 25

name 3 types of cartilage

Answer 25

hyaline cartilage, elastic cartilage, fibrocartilage

Question 26

describe the structure of cartilage

Answer 26

synthesised by chondrocytes, contains:
type 2 collagen
chondroitin suplhate
keratan sulphate
hyalraunic acid

Question 27

is cartilage vascular or avascular?

Answer 27

avascular

Question 28

which type of cartilages contain collagen fibres

Answer 28

fibrocartilage (abundant) and hyaline (few)

Question 29

what can over/under production of ECM cause?

Answer 29

over-production = fibrosis
over-degredation = osteoarthritis

Question 30

how is marfans disease caused by an ECM abnormality?

Answer 30

a fibrillin-1 gene mutation affects skin CT, bone, and vessels
results in vision problems, heart defects, long/slender limbs, fingers and toes

Question 31

what is alport syndrome and what is it caused by?

Answer 31

mutation in collagen 4 genes, BM in glomerulus becomes defective and causes blood/protein in urine

Question 32

what is ehlers-danlos syndrome and what causes it?

Answer 32

due to collagen 1/3/5 mutations, results in abnormal collagen production resulting in hypermobility and stretchy, fragile skin