Extra cellular matrix biology I Flashcards
What are the functions of the Extracellular matrix
- Provides physical support
- Determines the mechanical and physicochemcial properties of the tissue
- Influences the growth, adhesion and differentiation status of the cells and tissues with which it interacts
- Essential for development, tissue function and organogenesis
Define extracellular matrix
Complex network of proteins and carbohydrates which forms the insoluble component of the extracellular environment
What are the three main components of the ECM? Give some examples of each.
Collagen – e.g. collagen type I, type II and III (fibrillar) collagen type IV
Multi-adhesive glycoproteins – fibronectin, fibrinogen and laminins
Proteoglycan - aggrecan, versican, decorin and perlecan
Which of these substances are only found in the basement membrane?
Collagen type IV Laminin Perlecan
A mutation in the gene encoding which ECM compound causes each of the following disease: Osteogenesis Imperfecta Marfan's Syndrome Alport's Syndrome Epidermolysis bullosa Congenital Muscular Dystrophy
what part of the ECM does it affect
Osteogenesis Imperfecta– Type 1 Collagen
Marfan’s Syndrome– Fibrillin 1
Alport’s Syndrome– Type IV Collagen Epidermolysis bullosa– Laminin 5 (all three chains)
Congenital Muscular Dystrophy– Laminin 2 (alpha 2 chain)
Affects the matrix protein
Give an example of a disease that affects ECM catabolism and the protein affected
Hurler’s Syndrome – L-alpha-iduronidase Other mucopolysaccharidoses- inability to degrade GAGs (glycosaminoglycans)
What are the features of connective tissues?
Rich in ECM.
Contains ECM + component cell e.g. macrophages
Give an example of a disease caused by excess deposition of ECM.
Liver fibrosis Lung fibrosis- Silicosis
Kidney Fibrosis- diabetic nephropathy
Give an example of a disease caused by excessive loss of ECM
Osteoarthritis
Describe the arrangement of collagen fibres in skin, mature bone and eyes and explain its significance.
Successive layers are at right angles to each other so it can resist tensile force in all directions
What is the structure of a collagen molecule and what is it?
-It is a family of fibrous proteins, found in all multi-cellular organisms. Most abundant protein
It is a stiff triple helix consisting of three alpha chains Every third amino acid is glycine because only glycine is small enough to fit in the inside of the triple helix. The other two amino acids are commonly proline and hydroxyproline, which form interchain hydrogen bonding that contributes to the structural integrity of collagen.
-each alpha chain forms a helix, each helix wraps around eachother to form a stiff triple helical structure, indiviual triple helices forms FIBRILS which come together to form COLLAGEN FIBRES.
Describe the biosynthesis of collagen.
Collagen is made as procollagen in the endoplasmic reticulum.
•Procollagen has N and C region which are NOT in triple helices.
•Once outside the cell-the N and C propeptides are removed in fibrillar collagen but remain part of the collagen in most other collagen by extracellular peptidases.
•The collagen is then released and forms fibrils laterally with cross-‐linkages between collagen molecules in the fibril, providing strength and stability.
What is important of the way collagen fibrils are positioned
The alignment of the collagen fibrils determines which directions the tissue can resist tensile force in.
What is the importance of hydroxylation of proline and lysine in collagen structure?
It allows interchain hydrogen bonding that contributes to the structural integrity and stability of the collagen fibre.
Lysine and hydroxylysine is also modified in the formation of covalent cross-linkages after the collagen is secreted – this helps provide tensile strength and stability
What two other substances are needed for hydroxylation of proline and lysine
Hydroxylation is carried out by Prolyl and Lysyl Hydroxylases- this requires Vitamin C and Iron
What does a lack of vitamin C mean
Lack of proper collagen hydroxylation which can’t aggregate together properly to form solid fibres ‐affects tissue stability (scurvy)
What are the collagens that don’t form fibrils?
Fibril-associated collagens (e.g. collagen IX+type XII) which is involved in the organisation and size of collagen fibrils
Network forming collagens – e.g. collagen IV (basal lamina). Type IV collagen assembles into a sheet-like network.
the collagen type IV molecules can associate laterally between triple-helical segments as well as head-to head and tail-to tail between the globular domains to give dimers, tetramers and higher order complexes.
Describe the composition of Elastic fibres.
They consist of an elastin core and microfibrils around the outside that are rich in fibrillin
What causes Marfan’s syndrome and what are some clinical features of Marfan’s Syndrome?
Gene mutation in fibrillin 1 Longer arm span than height – long fingers and toes – predisposed to aortic ruptures
What is the general structure of elastin?
It consists of a hydrophobic region and an alpha-helical region (which is rich in alanine and lysine. Many lysine side chains are covalently cross-linked.) Changes configuration when stretched and goes back to normal when stress is removed (like rubber band).
What are Basement membrane made of
Collage IV and Laminins are the major components. It is a special type of ECM
What is diabetic Nephropathy
ECM accumulation
- Impinging on capillaries
- restricts renal filtration leading to renal failure.
How do you best describe connective tissues?
What are the functions of basement membranes?
Tissues rich in extracellular matrix with sparse cells.
Separating cells from connective tissue
