Extracellular Matrix Flashcards
ECM (extracellular matrix)
- the non-cellular component present within all tissues and organs
- a complex network of proteins and polysaccharides
- secreted locally by cells and remain closely associated with them
- provides structural, adhesive and biochemical signalling support
Types of ECM
- two types- interstitial connective tissue matrix: surrounds cells and provides structural scaffolding for tissue. Basement membrane: separates the epithelium from surrounding stroma
Where is ECM found
- bone, tendon, cartilage, blood vessel walls, vitreous body of the eye, cornea, dermal layer is skin and basement membrane
Function of ECM
- provides mechanical and structural support
- tensile strength and determines cellular micro environment
Cellular micro environment of ECM
- anchor cells (through cell-ECM junctions)
- influences embryonic development
- provides pathways for cellular migration
- sequesters growth factors
- provides a residence for roaming phagocytic cells
- established and maintains stem cell niches
Acellular components (extra cellular matrix)
-fibres: collagen and elastin
-ground substances: proteoglycans, glycosaminoglycans, glycoproteins
Acellular component of tissue
- collagen, elastin, proteoglycans, hyaluronan, other glycoproteins
Collagen
- major insoluble fibrous protein in the ECM
- at least 28 different collagen occur in vertebrates
- structure: 3 collagen polypeptides from a triple helix, Gly-X-Y repeat motif
Types: fribrillar (type I and II) skin, tendon, bone -> strength
Sheet/network- forming (type IV) basement membrane-> support/filter
Elastin
- structural protein arranged as fibres
- abundant in tissue that require stretch and recoil properties
- assembly into functional fibres requires the presence of a structural glycoprotein- fibrillin
Elastin
- structural protein arranged as fibres
- abundant in tissue that require stretch and recoil properties
- seem my into functional fibres requires the preened of structural glycoprotein- fibrillin
ECM arrangement in connective tissue
- lose irregular connective tissue- lymphoid tissue
- dense irregular connective tissue- dermis
- specialised: dense regular, bone and cartilage
Ground substances
- an amorphous, colourless, gelatinous material
- fills space between fibres and cell- consists of large molecules called glycosaminoglycans (GAGs) which link together with core protein to form even larger molecules called proteoglycans
- very good at absorbing water (90% of EXM is made up of water)
- resistant to compressive forces
- extremely hydrophilic
- adopt extended conformations water-swollen 3D network
- enables matrices to withstand high compressive forces
Glycosaminoglycans
- also called mucopolysaccharides
- chains of repeating disaccharide units
- carbs component of prteoglyxans
- attracts water: gel/cushioning and hydrating properties
Proteoglycans
- also know as mucoproteins
- protein core + GAGs-> bottle brush structure
-90-95% carb GAG
ECM synthesis of fibres: glycogen
- synthesised as procollagen
- post translational modification: glycosylation and hydroxylation
- protein assembly: triple helix
ECM synthesis of fibres: elastin
- synthesised as: tropoelastin
- post translational modification: hydroxylation
-protein assembly: fibrillin scaffold cross-linked fibres
Proteoglycan
- core protein synthesised on rER
- addition of polysaccharide as disaccharide repeats in Golgi
- delivered to extracellular compartments by exocytosis
- assembly with other ECM components
Deregulated ECM remodelling
- ECM synthesis: hyperproliferation of fibroblasts; excess ECM-> fibrosis, embryo genesis and angiogenesis
- pathogen-> collagenase-> invasion of host bacteria
-excess activation-> matrix metalloproteinases (MMPs)-> tumour cell invasion
Functions of basement membrane
- support
- binding of underlying connective tissue
- mediates signals between cells and connective tissue
- determines cell polarity
-permits flow of nutrients - path for cell migration
- barrier to downward growth
Disorders of basement membrane
- cancer: epithelial tumours regarded as malignant once BM is breached
- diabetes mellitus: thickening of BM in glomerulus changes permeability
- epidermolysis bullosa: attachment of epidermis to BM
- good pastures syndrome: autoantibodies to collagen IV destroy BM in glomerulus and lung
Bone cells
- osteoblasts: matrix production
- osteoclasts: matrix resorption
- osteocyte: maintenance
Cartilage
- synthesised by Chondrocytes
- formed from type II collagen
Contains - chondroitin sulphate
- keratan sulphate
- hyaluronic acid
Types of cartilage
Hyaline cartilage- avascular, few viable collagen fibres, has perichondruim, found in nasal septum, articulate surfaces
Fibrocartilage- abundant collagen fibres, avascular, no perichondruim, found in IV discs, sternoclavicular joint
Elastic cartilage- contains elastic fibres, avascular, had perichondruim, found in external ear, epiglottis and auditory tube
When ECM goes wrong
- over degradation: osteoarthritis
-over production: fibrosis
When ECM goes wrong, conditions
Elastin- SVAS, arterial defects
Fibrillin-1- Marfan syndrome: skeletal, ocular and cardiovascular abnormalities
Collagen I- Ehlers-Danlos Syndrone: joint and skin abnormalities
Collagen IV: alport syndrome (chronic kidney disease) and Goodpasture disease (glinerulonephritis and pulmonary haemorrhage)
Marfan syndrome
- affects connective tissue of skin,bone, blood vessels and many other organs and tissue
- mutations in fibrillin gene, autosomal dominant
- vision problems (lens dislocation)
- heart/aortic defects
- abnormally long and slender limbs, fingers and toes
Alport syndrome
- BM in the glomerulus of kidney forms a part of the selectively permeable glomerular filtration barrier
- mutation in collagen IV genes
