ECM 1 Flashcards
ECM Definition
A complex network of proteins and carborhydrates filling spaces between cells. This has both fibrillar and non-firbrillar components
ECM Functions
- physical support
- determines the mechanical and physicochemical properties of the tissue
- influences the growth, adhesion and differentiation status of the cells it interacts with
- essential for development
Connective Tissue Components
- Collagens e.g. Type 1,2,3 (fibrillar) and type 4 (basement membrane)
- Multi-adhesive glycoproteins e.g. fibronectin, fibrinogen and laminins (basement membrane)
- Proetoglycans e.g. aggrecan, versican, decorin and Perlecan (basement membranes)
Osteogenesis Imperfecta Cause
Type 1 Collagen Gene Mutation
Marfans SYndrome Cause
Fibrillin 1 Gene Mutation
Alports Sybdrome Cause
Type 4 Collegen (alpha 5) Gene Mutation`
Epidermolysis Bullosa Cause
Laminin 5 Gene Mutation (in all 3 chains)
Congenital Muscular Dystrohpy Cause
Laminin 2 (alpha 2 ) Gene Mutation
Hurlers Syndrome Cause
L-alpha-iduronidase Gene Mutation affecting ECM catabolism
Excessive loss of ECM?
Osteoarthritis
Excessive deposition of ECM?
- cirrhosis
- kidney fibrosis
- lung fibrosis
Basement Membrane Componensts
- collagen 4
- laminins
- perlecans
Number of collagen genes
42 genes
Collagen composition
3 alpha chains forming a triple helix
Type 1 = (a1(I))(a1(I))(a2(I))
Type 2 = (a1(II)) x3
Type 3 = (a1(III)) x 3
Glycine in Collagen position
every 3rd position
Collagen Biosynthesis
Pro-collagen (N and C propetides removed once oustide the cell) —> Collagen —> fibril —-> cross-linking —-> fibre
Hydroxyl Group Function
Normally formed on lysine and proline. They contribute to the Hydrogen bond formation. Lysine + hydroxy are modified in covalent cross-link formation.
What do hydroxylases require to function?
Vitamin C and Iron (Fe2+)
Fibril-Associated Collagen Names and Function
Type IX and XII and these associate with fibrillar collagens and regulate the organisation and size of collagen fibrils.
Elastic Fibres Function
- elasticity of tissues
- elasticitiy of skin, blood vesselsand lungs.
Elastic Fibres Structure
= Elastin Core + Microfibrils.
Microfibrils are rich in protein Fibrillin
Elastin Structure
- Two segments: Hydrophobic regions and alpha-helical regions (rich in alanine/lysine)
- many lysine side chains are covalently cross-linked.
Basement membrane function
They surround muscle, peripheral nerves and fat cells as well as underlying most epithelia. Used for the seperation of cells from the underlying connective tissue
Basement Membrane Example
e.g. Glomerulus - basement membrane prevents macromoleculs from the blood into the nephron. This can result in diabetic nephropathy with ECM accumulation.
