Week 3- Extracellular Matrix Flashcards
What is the extracellular matrix?
A complex of macromolecules deposited by cells, contains fibrillar and non fibrillar components
What is the function of the extracellular matrix?
Mechanical stability and support, also influences cell behaviour (growth, differentiation, status of tissue)
What do connective tissues contain?
Collagen, adhesive glycoproteins, proteoglycans, cellular components. Differ in what they contain and orientation of collagen eg vitreous humour vs tendon vs cartiledge
Describe the structure of collagen
Made of 3 alpha chains that wind together to form a helix, every 3rd amino acid is glycine as its the smallest amino acid, a fibrous protein. It provides tensile strength and stability
How many types of collagen are there and how do they differ?
Type 1- heterodimer, contains chains from 2 different genes
Type 2 & 3- homodimer, contains chains from only 1 gene
What are some post translational modifications undergone by collagen?
Hydroxylation of proline and lysine, lysine hydroxylation allows intramolecular cross linkages (only after collagen is secreted)
What happens to collagen if someone has scurvy?
A lack of vitamin C means hydroxylation cannot occur causing low tissue stability due to less cross links
Describe the biosynthesis of collagen
Collagen chains are first manufactured as longer pro alpha chains that fold into triple helical procollagen molecules before release.
How do collagen fibers assemble?
Tropocollagen molecules are staggered to form fibrils. Their parallel nature means they resist force in one direction, making them stronger
What symptoms of Ehler’s Danlos syndrome is related to skin?
A mutation in collagen can result in stretchy and loose skin
What is special about type IV collagen?
It doesn’t form membranes
What is the basement membrane?
A membrane that underlies epithelia, surround smooth muscle + peripheral nerves + fat cells. In kidneys it forms the glomerular basement membrane
How does diabetic neuropathy affect basement membranes?
There is a thickening of the basement membrane due to extra deposition of extracellular matrix restricting renal filtration and leading to kidney failure
What happens in Alport syndrome?
Splitting of the glomerular basement membrane causes loss of kidney function and hearing loss
Describe the structure of elastic fibers
Contain a core of elastin (a protein made of 2 alternating regions- hydrophobic and alpha helical, the latter of which is rich in alanine and lysine with lysine forming covalent crosslinks) and microfibrils rich in the protein fibrillin
What happens in Marfans syndrome?
A mutation in the gene for fibrillin 1 protein causes skeletal and ocular problems
What are proteoglycans?
A core protein to which are attached GAG chains
Describe the structure of GAG chains
They are made of real eating disaccarides of which at least one is an amino sugar (a sugar where the hydroxyl group is replaced by an amino group). Many are sulphated or carboxyalted giving them a negative charge so water moves into the ECM. Swelling pressure is negated by collagen fiber tension.
What are the 4 main groups of GAG chains
Hyaluron
Dermatan phosphate
Keratan phosphate
Heparan phosphate
Describe the structure of hyaluron
A carbohydrate chain without any core proteins, can undergo lots of polymerization and become large so it has a high viscosity
Describe the structure of aggrecan
Major component of cartilage in the ECM, GAGs are very highly sulphated so high negative charge and draws lots of water in
What happens in osteoarthritis?
Erosive degradation of ECM leading to loss of cartiledge cushioning. As age increases aggrecan is cleaved by aggrecanases
What happens in fibrotic disease
Excessive production of fibrous tissue
