Tissues 3-Extracellular Matrix Biology I Flashcards
Describe the extra cellular matrix and its role (3)
A complex network of protiens and carbohydrates filling spaces between cells. Consists of non fibrillar and fibrillar components
Role:
Physical support
Determines mechanical and physio chemical properties of cells
Influences growth, adhesion and differenation status of cells
Molecules in the ECM can interact with receptors on the cell surface
you need ECM for multi cellular life
What are the components of connective tissue
ECM
Collagens
Type I, II and III (fibrillar)
Type IV (basement membrane)
Multi-Adhesive Glycoproteins
Fibronectin, Fibrinogen
Laminins (basement membrane)
Proteoglycans
Aggrecan, Versican, Decorin
Perlecan (basement membrane)
What are the 4 categories of disorders/mutations that lead to abnormalities in ECM
Gene mutations affecting matrix proteins
Osteogenesis Imperfecta - Type I Collagen
Marfan’s Syndrome - Fibrillin 1
Alport’s Syndrome - Type IV Collagen (a5)
Congenital Muscular Dystrophy - Laminin 2 (a2 chain)
Gene mutations affecting ECM catabolism
Hurler’s Syndrome - L-a-iduronidase
Other mucopolysaccharidoses - inability to degrade GAGs (glycosaminoglycans)
Fibrotic disorders due to excessive ECM deposition
Cirrhosis
Kidney Fibrosis - diabetic nephropathy
Lung Fibrosis - silicosis
Disorders due to excessive LOSS of ECM
Osteoarthritis
Describe Vitreous Humour
Jelly that fills the interior of the eye
Soft and transparent
Describe the alignment of collagen fibrils
Different layers of collagen fibrils are laid down nearly parallel to each other
This gives the tissue TENSILE STRENGTH - the ability to resist stress and not snap.
This can resist tensile force in two directions.
Skin - successive layers are at right angles to each other.
Same arrangement in mature bone and in the cornea.
This gives the tissue the ability to resist tensile force in all directions.
IMPORTANT CONCEPT - The alignment of the collagen fibrils determines which directions the tissue can resist tensile force in.
Describe the structure of Collagens
There are 42 genes encoding collagens in humans.
EACH COLLAGEN MOLECULE COMPRISES OF THREE a CHAINS - FORMING A TRIPLE HELIX
Type I collagen has chains from two different genes - its composition is [a1(I)]2 [a2(I)]
Types II and III collagen have only one chain type
What is the third amino acid in collagen
Every third position must be a GLYCINE - this is the only amino acid small enough to occupy the interior of the triple helix
What is procollagen, where is it made and how is it modified
Collagen is made as procollagen in the endoplasmic reticulum.
Procollagen has N and C regions which are NOT in triple helices.
Once outside the cell - the N and C propeptides are removed.
The collagen is then released and forms fibrils with cross-linkages between different collagen molecules
What is hydroxylation of collagen and what does it require
adding a hydroxyl group on lysine and proline so that you get interchain hydrogen bonds
This is done by hydroxylases
Hydroxylases require iron (fe 2+) and vit c
without vit c collagen cant aggregate properly and solid fibres arent formed
which collagens don’t form fibrils
Fibril-Associated Collagens - e.g. Type IX + Type XII - associate with fibrillar collagens and regulate the organisation and size of collagen fibrils.
Network-Forming Collagen - Type IV - present in all basement membranes - molecular constitution varies from tissue to tissue.
Type IV collagen assembles into a sheet-like network - it is an essential component of basement membranes.
What is Marfan’s Syndrome
Marfan’s Syndrome - mutation in FIBRILLIN-1
Manifestations primarily involve the skeletal, ocular and cardiovascular systems.
arm-span which is longer than their height.
Predisposed to aortic ruptures.
Describe Elastin
Two types of segment: Hydrophobic regions and a-helical regions (rich in alanine and lysine)
Elastin is like a rubber band - it changes its configuration when stretched, when the stress is removed, it will return to its original configuration.
Basement Membranes
They are flexible, thin mats of ECM.
surround muscle, peripheral nerves and fat cells and underlie most epithelia.
GLOMERULUS function - Basement membrane prevents macromolecules going from the blood into the nephron.
What is the role of basement membranes on Diabetic nephropathy
ECM accumulation - Impinging on capillaries - restricts renal filtration - RENAL FAILURE.
