Extracellular Matix Flashcards
What are the functions of the Extracellular matrix?
Physical support
Determines mechanical and physiochemical properties of tissue
Influences growth, differentiation and adhesion of different tissues
What are the components of connective tissue?
Collagen fibres
Macrophages, fibroblasts etc.
Multi-adhesive glycoproteins (fibrinogen/laminins)
Proteoglycans (Aggrecan, versican, decorin)
What is connective tissue?
Seperates and holds together other tissues.
Contains few cells and lots of ECM
What matrix protein gene mutation does Osteogenesis imperfecta effect?
T I Collagen
What matrix protein gene mutation does Marfan’s effect?
Fibrillin 1
Mutation in fibrillin-1 leads to loss of integrity of elastic fibres because fibrillin has not formed properly; tall and skinny with predisposition to aortic rupture
What three disorders are due to excessive ECM deposition?
Cirrhosis - Liver fibrosis
Diabetic neuropathy - kidney fibrosis
Silicosis - Lung fibrosis
What disease results from excessive loss of ECM?
Osteoarthritis
What disease is caused by mutations affecting ECM catabolism?
Hurler’s syndrome
What percentage of body weight is collagen?
25%
How many types of collagen are there in humans, and how many genes code for them?
28 by 42 genes
What is the molecular structure of collagen?
Three alpha chains forming left-handed triple helix
What is every third amino acid in collagen and why?
Glycine, as its the only one small enough to occupy the interior
What is Type I collagen made of? How is this written?
2x alpha 1 and 1x alpha 2
[a1(I)]2 [a2(I)]
What is the organisation of collagen?
Trip helix forms 10-30nm fibril, arranged into 0.5-3um fibres
Describe collagen biosynthesis
Procollagen synthesised first, with N and D terminal propeptides at each end; these are cleaved upon release from cell, allowing collagen to form fibrils; covalent cross links then form between fibrils to form fibres
What does Vit C deficiency result in?
Underhydroxylated Collagens - scurvy
Describe how different arrangements of collagen in different tissues give specific functions
Tendons: strands run parallel so provide tensile strength in one direction
Skin: cross over each other, providing more universal tensile strength
What type of collagen is found in the basement membrane?
Type IV - dimers and tetramers form complex sheet network
What do elastic fibres do, and how?
Give tissues elasticity e.g. Blood vessels, lungs and skin; collagen and elastic fibres often interwoven to limit the extent of stretching; consist of elastin core with microfibrils rich in fibrillin
What do laminins do?
Have many NH2 groups to bind to other molecules in basement membrane
E.g. Integrins, dystroglycan, perlecan, nidogen
What is the structure of Laminin?
Alpha, beta, gamma chains in crucifix shape. Coiled-coil domain in long bit
What can congenital muscular dystrophy be caused by?
Absence of alpha2 chain in laminin 2.
Hypotonia, weakness, joint deformaties from birth
Where are laminins found?
Basement membrane only
Where are fibronectins found?
Connective tissue (not BM)
