ecm Flashcards
what are the causes and symptoms of osteogenesis imperfecta?
defective collagen type 1 synthesis
point missense mutation
glycine –> bulkier amino acid
fragile bones, blue sclera, weak tendons, thin skin
what is the inheritance pattern of type 1 osteogenesis imperfecta?
autosomal dominant
what are the two types of osteogenesis imperfecta and how severe are they?
OI 1 - mildest and most common
OI 2 - very severe, de novo, lethal
what causes Marfan’s syndrome?
mutant, misfolded fibrillin which causes elastin to be too stretchy
what are the symptoms of Marfans?
tall long arms and legs loose joints floppy cardiac valves eye problems aortic aneurysms spider fingers
what is the inheritance pattern of Marfan’s?
autosomal dominant
explain the cell migration model
actin filaments polymerise to change the shape of the cel
adhesion proteins attach at the leading edge
detach from trailing edge
what happens in cell migration on a flat surface with no ECM?
cell detachment and apoptosis
how do cancer cells impact cell migration and the ECM?
cleave cell adhesion molecules
break down ECM
growth factors and cytokines facilitate migration and metastasise
what are the functions of the ecm?
- Functions as adhesive substrate
- Provides structure
- Presents growth factors to their receptor
- Stores growth factors
- Senses and transduces mechanical signals
what is in ECM/
o Collagens
o Elastin
o Glycoproteins
o Proteoglycans
how are macromolecules secreted and how do they change outside of cells?
secreted as small precursors and they polymerise once outside cells
describe the structure of collage?
triple helix made up of glycine and either proline or hydroxyproline (every 3rd amino acid is glycine)
how much of the total body mass is collagen?
25%
how many types of collagen are there?
19
what are the 2 main families of collagen?
o Fibril forming – Type I, II and III
o Non-fibrillar – the rest
where is type 1 collagen found?
skin tendon bone most loose/dense CT ligaments
where is type 2 collagen found?
hyaline cartilage
where is type 3 collagen found?
lymphoid organs
where is type 4 collagen found?
basement membrane (along with type 6)
what is osteogenesis imperfecta?
brittle bone disease
what are the genes affected in type 1 osteogenesis imperfecta?
Chromosome 17, COL1A1 gene
Chromosome 7, COL1A2 gene
what is the mutation which causes osteogenesis imperfecta type 2?
new mutation - de novo
where is elastin found?
blood vessels, lungs, ligaments and dermis of skin
what is elastin made of?
glycine
proline
more valine than collagen
why do elastic fibres need fibrillin?
to stop them stretching too far
stability
helps anchor fibres to other ECM proteins
what effect does damage to fibrillin have on TGF-B?
causes more TGF-B to be released into the ECM so fibroblasts make more ECM
what are glycoproteins?
proteins with oligosaccharides attached
what are the roles of glycoproteins?
o Receptors on cell surface - Bacteria, viruses, toxins, hormones, other cells
o Strength and support to the ECM
o Slime layer of bacteria and flagella
what are the 2 main glycoproteins that help with cell adhesion?
fibronectin
laminin
what happens to your preoteoglycans as you get older?
o Smaller protein cores and fewer side chains
o Less water held drier CT more brittle and more likely to be damaged less shock absorbency
o Seen in IV disc
what can cause odema?
increased proteoglycan formation
what are the 5 major protein families that cell adhesion molecules belong to?
– Cadherins – interact with similar molecules on the other cell
– Ig Super family – interact with similar molecules on the other cell
– Selectins - selects and attaches a cell to the ECM
– Mucins – will attach to selectins
– Integrins – work with fibronectin and laminin
describe the basic principles of cell migration on a 2D surface?
- polymerisation of actin filaments at leading edge gives a protrusive force
- senses environment as it proves forward
- moves in direction of growth factors
- new cell adhesion molecules at the front
- adhesion molecules detach from the back
- • Forces produced by contractile network combined with actin filament and disassembly help to retract the trailing cell edge.
describe cell migration on a 3d fibrillary ecm?
- Cell has to force its way through scaffold of collagen and elastin fibres – not unidirectional movement
- If ECM is nicely lined up like in dense regular CT, then the cell can just push itself in one direction
- If dense irregular or loose CT then its more likely to have an amoeboid movement.
what are the steps of leukocyte extravasion?
“chemoattraction”, “rolling adhesion”, “tight adhesion” and “(endothelial) transmigration” (amoeboid movement through basement membrane to get to ECM).
how do cells migrate in cancer?
- Cancer cells produce proteins which break down the cell adhesion molecules.
- Loosens cancer cells within the tumour cells, allowing them to break off.
- Go through rolling movement and can break down ECM holding cells together.
- Degradation of ECM allows invasive cells to migrate into surrounding tissue and vasculature
- Activation of growth factors and cytokines increases cell migration and likelihood of metastasis
