Extracellular Matrix Biology I Flashcards
What’s the Extracellular Matrix?
A COMPLEX NETWORK OF PROTEINS AND CARBOHYDRATES FILLING SPACES BETWEEN CELLS
It consists of both fibrillar and non-fibrillar components.
You need extracellular matrix for the existence of MULTICELLULAR LIFE
Functions of the ECM?
Physical Support
Determines the mechanical and physicochemical properties of the tissue
Influences the growth, adhesion and differentiation status of the cells with which it interacts.
Essential for development - tissue function and organogenesis
What is Connective Tissue?
Connective Tissue = Extracellular Matrix + Component Cells
Connective tissue is rich in extracellular matrix
Basal Lamina - separates epithelial cells from the underlying connective tissue
Macrophages are present in connective tissue
Components of Connective Tissues?
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)
Which are only found in the Basement Membrane?
Collagen - Type IV
Multi-adhesive glycoproteins - Laminins
Proteoglycans - Perlecan
Gene mutations affecting matrix proteins
Osteogenesis Imperfecta - Type I Collagen
Marfan’s Syndrome - Fibrillin 1
Alport’s Syndrome - Type IV Collagen (a5)
Epidermolysis Bullosa - Laminin 5 (in all 3 chains)
Congenital Muscular Dystrophy - Laminin 2 (a2 chain)
Fibrotic disorders due to excessive ECM deposition
Cirrhosis
Kidney Fibrosis - diabetic nephropathy
Lung Fibrosis - silicosis
Disorders due to excessive LOSS of ECM
Osteoarthritis
Describe different properties of connective tissues?
Tendons + Skin = Tough and flexible
Vitreous Humour = Soft + Transparent jelly that fills eye interior
Bone = Hard and Dense
Cartilage = Resilient and Shock-absorbing.
Collagen Overview?
A family of fibrous proteins found in all multicellular organisms. 28 different collagens.
The most abundant protein in mammals - 25% of total protein mass
Major proteins in bone, tendon and skin
Function of Collagen?
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.
Collagen Structure?
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 – their compositions are, therefore, [a1(II)]3 and [a1(III)]3
Each a chain forms a helix and each helix wraps around each other. each a chain is ~1000 amino acid
Three a chains form a STIFF TRIPLE HELICAL STRUCTURE. Every third position must be a GLYCINE - this is the only amino acid small enough to occupy the interior of the triple helix.
Collagen Biosynthesis?
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.
Lysine and Proline Hydroxylation
Hydroxyl group is important because it contributes to interchain hydrogen bond formation.
Lysine and hydroxylysine are also modified in the formation of covalent cross-linkages. This takes place after the collagen is secreted.
Hydroxylation is carried out by Prolyl and Lysyl Hydroxylases
VITAMIN C and IRON (Fe2+) to function.
Which collagens dont form 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.
