ECM Flashcards
define the ECM
a complex network of secreted macromolecules in the extracellular space
The 4 categories of substances found in the ECM are
- organic fibrillar matter
- organic non-fibrillar matter
- ions
- water
organic fibrillar matter means
elastin, fibrillin, laminin, fibril-forming collagens
organic non-fibrillar matter means
fibronectin, proteoglycans, and lattice forming collagens
ions in the ECM are bound to
negatively charged GAG
ECM macromolecules are synthesized by
cells of mesenchymal origin such as: fibroblasts, sm cells, chondroblasts, osteoblasts, epithelial cells
fibronectin and laminin are
structural glycoproteins
collagens account for x% of total protein mass
30%
functions of the ECM
- provide support and anchoring for cells
- regulates polarity, differentiation, adhesion, migration, proliferation
- acts as organiser for tissue growth, regeneration, maintenance of tissue structure
- provides for inter-cellular exchange of metabolites, ion, water
the amount of ECM is a constant?
No, it varies depending on tissue types, developmental stage, pathological status
collagen is produced by
fibroblasts, osteoblasts, chondroblasts
the basic unit of collagen is
tropocollagen, which is a triple helix formed by 3 alpha polypeptide chains, enriched in glycine and Pro,HydroxyPro. They do not contain Cys, Trp
each tropocollagen alpha chain has x aa
1000
how many types of collagen are there
28
which direction is the helix turn of one of the tropocollagen alpha chains
left-handed helical structure
what direction is the helix turn once all three alpha chains are bound together
right handed triple helix
the repeated aa sequence of collagens is
glycine, proline, hydroxyproline. (The side chains of the Pro/Hyp form lateral interactions with other triple helices)
the H bonds in the CTH are between
NH2 group of Gly residues on one chain, and the CO group of the Pro/Hyp residues on neighbouring chains
what collagen types are fibril forming
1, 2, 3, 5, 11
most common types of collagen are
1: skin, tendon, heart, bone
2: cartilage
3: reticular CT
4: forms basal lamina, epithelium secreted layer of basement membrane
5: cell surfaces, liver, cornea, mucosa
list the types of non-fibrillar collagens
- network forming (4, 8, 10)
- facit (9, 12, 14, 16, 19)
- anchoring collagens (7)
- short chains (8, 10)
- multiplexin (15, 18)
- macit (13, 17)
how are type 1 collagens structured
each triple helix is displaced by 1/4 length (35nm) from its neighbour This is called a quarter staggered array. This helps form the banded pattern of collagen.
how are type 1 collagen fibrils assembled?
it is determined by chain recognition sequence in the C - propeptide
descemets membrane in the cornea is made of what type of collagen
VIII
the basement membrane of glomerulus of kidney is formed by
type IV
anchoring collagens connect x to y
epithelium to stroma
beaded filament forming collagens form
structural links with cells, are type VI, it is crosslinked into tetramers that assemble into microfibrils
elastin is found in what tissues
arteries, lungs, bladder, skin, elastic ligaments, cartilage
how many genes are present for elastin
one, it contains Gly, Val, modified Ala and Pro. tropoelastin does not contain hydroxylysine nor is it glycosylated
note
The lysines are involved in intermolecular crosslinking, while the week interactions between valine residues in the hydrophobic domains impart elasticity to the molecule.
• Tropoelastin is highly cross-linked to form insoluble complexes.
what does lysyl oxidase do
converts amine groups of lysine to form reactive aldehydes, this results in spontaneous formation of desmosine cross links
structure of elastin
is made of elastin fibers (made of a core region enriched in elastin proteins surrounded by microfiber sheath)