MBC - Extracellular matrix Flashcards
What is the ECM
A complex network of macromolecules (proteins and carbohydrates) deposited by cells, and then becomes immobilised to fill up the spaces between cells.
What cells deposit the components of the ECM
Fibroblasts
What components is the ECM composed of
Fibrillar and non fibrillar components
What is the purpose of the ECM
Development, tissue function and organogenesis.
Determines mechanical and physiochemical tissue properties.
What does the ECM influence in cells due to the combination of its components
Growth, adhesion and differentiation of cells
What are the three main components of the ECM
Collagens
Multi-adhesive glycoproteins
Proteoglycans
What types of collagen are found in the ECM
I, II, III, IV
What is type I collagen used for
Bone, skin and tendons
What is type II collagen used for
Cartilage
What is type III collagen used for
Fibrillar, found in blood vessels and reticulin (type of connective tissue fibre)
What is type IV collagen used for
Basement membrane
What glycoproteins are found in the ECM
Fibrinogen
Fibronectin
Laminin (basement membrane)
What proteoglycans are found in the ECM
Aggrecans
Versicans
Perlecans (basement membrane)
Decorin
How do we get a wide variety of connective tissue in the ECM?
We get different types of collagen and different collagen orientations interacting with different components of the ECM.
What do matrix components interact with to influence the cell physiochemical behaviour?
Cell surface receptors (integrins).
What is collagen?
Collagen is a family if fibrous proteins found in all multicellular organisms
Explain the synthesis of collagen
Follows the normal pathway for secreted protein:
Pro-alpha chains are secreted by the rER ribosomes
These then undergo a series of covalent modifications, and 3 chains form a pro collagen molecule.
The pro collagen molecule then undergoes cleavage and fibril formation to become a collagen fibre, which can then cross link with other collagen fibres.
What is a homotrimer?
This is a collagen molecule made up of three identical alpha chains. For example, type II and III collagen are made up of 1 chain type.
What is a heterotrimer?
Collagen molecule made up of at least 2 different a chains. Type I collagen is made up of different chains.
What does [α1(I)]2 [α2(I)] mean in type I collagen?
This means that the collagen molecule consists of 2 alpha-1 chains, and 1 alpha-2 chain.
What arrangement to a-chains typically have?
Gly-x-y
Why do a-chains have a gly-x-y arrangement?
Glycine is required at every third position as it is the smallest amino acid (only has H as its side group) so it can face inwards when the a chains are intertwined.
What are the x-y in the a-chain arrangement?
x - typically proline
y- typically hydroxyproline
Why is the hydroxylation of proline important?
This is an important post translational modification as it contributes to the H bonds between chains
When does cross linking occur
After collagen has been secreted
What other molecular residues are involved in cross linking?
Lysine and hydroxylysine.
How does vitamin C deficiency cause scurvy?
Prolyl and lysyl hydroxyls require vitamin C as a cofactor however deficiency leads to underhydroxylated collagens and thus unstable tissue thus scurvy.
Are all collagens fibril-related?
No, for example collagen IV is associated with the basement membrane, and its N and C termini are not cleaved.
What is Ehlers-Danlos syndrome
Stretchy skin and loose joints
What is the purpose of the N and C termini on type IV collagen
Essential for communication between and regulation of fibres
What is the basement membrane?
Highly specialised, thin sheets of ECM underlying epithelia and tubes.
What does the basement membrane contain?
Distinct collagens associated with proteoglycans and glycoproteins