Extracellular Matrix Flashcards
what is the ECM?
non-cellular component present within all tissues and organs
what are the 2 main types of ECM?
interstitial CT matrix - surrounds cells and provides structural scaffolding for tissues
basement membrane - separates epithelium from surrounding stroma
what is the composition and function of ECM?
complex network of proteins and polysaccharides
provices structure, adhesive and biochemical signalling support
where is ECM found?
bone, tendons, cartilage, blood vessel walls, vitreous body of the eye, cornea, dermal skin layer,
what are the 3 classifications of ECM function?
provides mechanical/structural support
tensile strength
determines cellular microenvironment
what is interstitial CT made of?
fibrous proteins (collagen/elastin)
ground substance (proteoglycans, glycosaminoglycans, glycoproteins)
describe the structure of collagen in ECM
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
explain the structure of elastin in ECM
fibrous structural protein
abundant in tissues requiring stretch and recoil properties
assemply into functional fibres requires presence of structural glycoprotein fibrillin
describe ECM arrangement in CT
loose irregular CT - lymphoid tissue
dense irregular CT - dermis
specialised - dense regular (tendons/ligaments), bone, cartilage
describe ground substsance
amorphous, gel-like, non-fibrous substance surrounding cells
describe glycosaminoglycan structure
chains of repeating disaccharide units, carb components of proteoglycans
attracts water giving it gel/cushioning and hydrating properties
very hydrophilic
describe proteoglycan structure
protein core + GAGs = ‘bottle-brush’ structure
90-95% carbs (GAG)
give 3 examples of glycoproteins in ECM and their function
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
explain the synthesis, PTMs and protein assembly of ECM fibrous proteins
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
explain the synthesis of ECM proteoglycans
synthesised on rER, addition of polysaccharide as disaccharide repeats in golgi, delivered to extracellular compartment by exocytosis, assembly with other ECM components
describe ECM remodelling
deposition -> degredation -> modification
(reversible)
give an example of deregulated ECM remodelling
excess activation of MMPs can cause a tumour cell invasion
explain ECM structure in epithelial tissue
the BM
thin, tough, sheet of ECM with a mat-like arrangement
describe the 3 ways BM can act on cells
lies underneath cells (epithelial/endothelial cells)
surrounds cells (muscle fibres)
separate 2 sheaths of cells (kidney and glomerulus)
what are the functions of BM?
support, binds to underlying CT, mediates signals between cells and CT, determines cell polarity, permits nutrient flow, cell migration path, downward growth barrier
give an example of a BM disorder
cancer - once BM is breached, epithelial tumours regarded as malignant
describe the ECM in bone
organic (30%) -> type 1 collagen (osteocalcin)
inorganic (70%) -> hydroxyapatite
ECM in bone - osteoid
name the 3 functional cell types in bone
osteoblast - matrix production
osteoclast - matrix resorption
osteocyte - maintenance
what does cartilage contain to become a proteoglycan?
aggrecan + hyalraunic acid
name 3 types of cartilage
hyaline cartilage, elastic cartilage, fibrocartilage
describe the structure of cartilage
synthesised by chondrocytes, contains:
type 2 collagen
chondroitin suplhate
keratan sulphate
hyalraunic acid
is cartilage vascular or avascular?
avascular
which type of cartilages contain collagen fibres
fibrocartilage (abundant) and hyaline (few)
what can over/under production of ECM cause?
over-production = fibrosis
over-degredation = osteoarthritis
how is marfans disease caused by an ECM abnormality?
a fibrillin-1 gene mutation affects skin CT, bone, and vessels
results in vision problems, heart defects, long/slender limbs, fingers and toes
what is alport syndrome and what is it caused by?
mutation in collagen 4 genes, BM in glomerulus becomes defective and causes blood/protein in urine
what is ehlers-danlos syndrome and what causes it?
due to collagen 1/3/5 mutations, results in abnormal collagen production resulting in hypermobility and stretchy, fragile skin
