Flashcards
Extracellular matrix and cell adhesion molecules
Cards in this deck (79)
- 1What is the ECM? What is the main role of the ECM?1) A complex network of secreted macromolecules
2) Hold cells in place - 2What does the ECM regulate? (4)1) Proliferation - regulated the amount of growth factors the cells/connective tissue see.
2) Differentiation
3) Migration - particularly important during development, also occurs in cancer (abnormal metastasis)
4) Cell-cell interaction - 3What are the five functions of the ECM?1) Functions as an adhesive substrate
2) Provides structure
3) Presents growth factors to their receptors
4) Sequesters and stores growth factors
5) Sense and transduce mechanical signals - 4How does the ECM function as an adhesive substrate? (2)1) Tracks to direct migratory cells
2) Concentration gradient for haptotactic migration - 5How does the ECM provide structure? (2) What happens during disease?1) Defines tissue boundaries
2) Provides integrity and elasticity to developing organs
3) Degraded by invasive cells during development and disease - 6What is the presentation of growth factors to receptors by the ECM important for? (2)1) Controls spatial distribution of ECM-bound surface molecules
2) Facilitates cross-talk between growth factor receptors and ECM receptors - 7What are the benefits of the ECM sequestering and storing growth factors? (3)1) Allows for spatio-temporal regulation of factor release
2) Organises morphogen gradients
3) Mediates release of factors in the presence of appropriate cell-mediated forces or proteolytic degradation - 8In what three ways does the ECM sense and transduce mechanical signals?1) Defines mechanical properties permissive/instructive to cell differentiation
2) Activates intracellular signaling through interaction with cell-surface receptors
3) Engages cytoskeletal machinery and synergises with growth factor signalling - 9What can result from injury to ECM?Release of growth factors or exposure of stem cells which were in a stem cell release (or allow cells to reenter the cell cycle)
- 10What are the macromolecules made by cells which are present in the ECM? (4)1) Collagens
2) Elastin
3) Glycoproteins
4) Proteoglycans - 11How are the macromolecules produced? Why?1) Constructed as precursors within the cells - fully form outside the cell
2) Because they are so large - 12What do the macromolecules form? In which structure are they more organised?1) 3D gelatinous bed for cells to live in
2) Tendons - 13What do changes in the ECM underly? Give specific examples1) Many chronic diseases
2) COPD
2) (Ischaemic) Cardiovascular disease
4) Lung fibrosis
5) Asthma - 14What are the types of cells which produce ECM? (2)Mesenchymal cells - fibroblasts
- 15What other cell types are found in the ECM?Plasma cells, macrophages, adipocytes, lymphocytes, blood supply, mast cells
- 16What forms the ground substance?The whole network of macromolecules plus the reticular fibres.
- 17What % of the total protein mass is collagen? What is 90% of that?1) 25% to 35%
2) Type I collagen - found in almost all connective tissues (very strong and robust) - 18How many different types of collagen are there?19-34
- 19What are the two families of collagen?1) Fibril forming
2) Non-fibrillar (mesh forming) - 20What is the classic structure of collagen?1) a-helix - three wind around each other
2) Every 3rd amino acid is glycine (in all collagen) - 21What tends to be linked to the glycine (especially in type I collagen)?Gly-X-Y (proline or hydroxyproline)
- 22Why is type 1 collagen so strong?The amino acids are very small - very tight packing
- 23How are the triple helices linked? What does this result in when looking down a microscope?1) Cross-linking to form a fiber
2) Stripy - 24Type I and type II collagen are...Fibril forming
- 25Where is type II found?Some types of cartilage - not as abundant as type I
- 26What are type IV and type VI collagen?Network forming -
- 27What does collagen type IV contribute to? (2)1) Glandular epithelium is embedded in type IV collagen
2) Basement membrane for epithelial cells. - 28What does FACIT stand for? What is the advantage of this? Which collagen types fall under this category?1) Fibrillar associated collagen interrupted triple helices
2) Triple helice at regular/irregular intervals is looser which allows it to bend.
3) Type IX, XII and XIV - 29Which collagens are transmembrane?Type XIII, XVII, XXIII, XXV
- 30Which collagen types are multiplexin?XVIII
- 31What is the mutation which makes FACIT loser?Amino acid rather than proline or hydroxyproline make the triple helix looser so that the collagen can bend
- 32What is/causes osteogenesis imperfecta?1) Brittle bone disease - defect in collagen type I. Individuals are more prone to having breaks. But also affects skin, teeth, tendons and ligaments (results in loose joints)
- 33What happens to the sclera in osteogenesis imperfecta?Sclera is very thin - can see the retina behind the eye so it looks blue
- 34What are the characteristics of osteogenesis imperfecta? (5)1) Fragile bones
2) Thin skin
3) Abnormal teeth
4) Weak tendons
5) Thin sclera - 35What underlies osteogenesis imperfecta?Single base chain - converts glycine to a more bulk amino acid - results in a loose section.
- 36What is the genetic inheritance pattern of type I osteogenesis imperfecta? What determines the severity? What % of OI cases does this account for? Type I is the X form of OI?1) Autosomal dominant
2) The type of amino acid which replaces glycine or proline
3) 50%
4) Mildest - 37Where do the mutations of type I OI occur? (2)1) Chromosome 17, COL1A1
2) Chromosome 7, COL1A2 - 38Which is the most severe form of osteogenesis imperfecta?Type II - babies are often born with fractures which occur during birth
- 39What type of mutation pattern does type II OI show?Usually de novo as babies don't usually survive - would be dominant otherwise.
- 40What is elastin required for?Flexibility in blood vessels (arteries especially), lungs, ligaments and skin
- 41In which way can elastin stretch?Two dimensions
- 42What happens after elastin has been stretched?Relaxes - returns to original form
- 43Describe the structure of elastin. (2) How does it differ to collagen?1) Rich in glycine and proline, neighbouring elastin fibres form cross-links.
2) Much more valine - 44What characteristic is valine largely responsible for?Very important for recoil due to the hydrophobic nature of valine
- 45What is elastin coated in? Why?1) Fibrillin
2) To limit the amount the elastin fibre can stretch - 46What causes Marfan syndrome?Fibrillin is misfolded - changes ECM and results in the less stability and increased stretch of elastin. Things that should be held in place can slip.
- 47Name a famous individual with Marfan syndromeAbe Lincoln
- 48What are the characteristics of Marfan syndrome? (7)1) Tall stature
2) Long arms and legs
3) Arachnodactyly (spider fingers)
4) Loose joints
5) Floppy cardiac valves
6) Eye problems (lens dislocation)
7) Aortic aneurysms (due to stretchiness of aorta in Marfans) - 49Aside from overstretching what's the other issue with misfolded fibrillin?Elastin may not be able to recoil properly.
- 50What does elastin control? What does it hold in place? Give an example. What effect does Marfan syndrome then have?1) Controls 3D network of ECM
2) Growth factors
3) TGF-B
4) Growth factors can 'pop' out and affect cells - can lead to increased growth/entry into cell cycle etc. - 51Describe the structure of a typical glycoprotein (3)1) Carbohydrate moiety (mannose and N-acetylglucosamine)
2) Extracellular domain - polypeptide chain
3) Hydrophobic amino acid domain which inserts in lipid bilayer
4) Intracellular domain - 52How many monosaccharides are attached to a protein in glycoprotein? Where is the sugar component usually? Protein?1) 200-300
2) Oligosaccharide sticks out into ECM
3) Protein is inserted into the lipid bilayer - 53What are the roles of glycoproteins? (3)1) Receptors cell surface
2) Strength and support to the ECM
3) Slime layer of bacteria and flagella - 54What is the function of the slime layer in bacteria?Hides them from immune system.
- 55Are glycoproteins embedded in the membrane or free?Both
- 56On what would you find a glycoprotein as a receptor? (5)1) Bacteria
2) Viruses
3) Toxins
4) Hormones
5) Other cells - 57What are two of the most important glycoproteins (apart from ECM)? At what stage can they be particularly important?1) Fibronectin and laminin
2) Development - can line migration routes - 58How do cells interact with fibronectin and laminin?Cell surface receptors can bind fibronectin
- 59What are the 5 roles of fibronectin?1) Cell adhesion
2) Cell migration
3) Cell shape
4) Cell differentiation - due to linkage with cell receptors
5) Cytoskeletal organisation - receptors embedded in the membrane are linked to the inside of the cell via actin - 60What class of receptors does fibronectin interact with?Integrins (which are embedded in the cell and bound on the internal side to actin)
- 61What are the three main roles of laminin/where is it usually found? (3)1) Cell adhesion - basement membrane (usually collagen 4 network) - epithelial cells linked to BM via laminin. Also important in skeletal muscle.
2) Cell migration (especially development)
3) Cytoskeletal organisation (links to shape of cell and helps to stabilise it in its external environment) - 62What are proteoglycans?Gel-forming component of ECM
- 63What do proteoglycans consist of? How do they compare to glycoproteins?1) Peptide chains (proteins) with covalently bound sugars (conjugated to polysaccharides with repeating units)
2) 95% carbohydrate i.e. much more sugar - 64What are the side chains in proteoglycans?Glycosaminoglycans and mucopolysaccharides
- 65What does the negative charge of the proteoglycan sugar side chain facilitate?Proteoglycans form large aggregates - forma jelly-like matrix; draws and holds water due to the negative charge of the GAG change.
- 66Why is the ability of water by proteoglycan aggregates so important?1) Hydrates the network and holds nutrients
2) Impressive compressive strength - 67How are proteoglycans affected by age/what are they generally important for?1) Involved with the health and maintenance of the ECM
2) As humans mature the size of proteoglycans reduces and the side chains become less numerous - this reduces the amount of water the proteoglycan is able to hold. - 68What affect does the age-related change in proteoglycans have?1) During injury there is an increase in water/swelling to help heal damage - drys out with age
2) The intervertebral disc is an important shock absorber - dries out with age - less able to able to take strain and is more likely to be damaged possibly resulting in herniated slipped dics. - 69What are the major cell adhesion classes? (4)1) Integrins
2) Ig superfamily members
3) Cadherins
4) Selectins - 70What are the four basic principles of cell migration?1) Polymerisation of actin filaments at leading edge give a protrusive force
2) New adhesions are rapidly linked to network of actin filaments
3) Combined activity of retrograde actin movement and contractile forces produced by stress fibre generates tension to pull cell body forward
4) Forces produced by contractile network combined with actin filament and disassembly help to retract the trailing age. - 71Describe the steps of cell migration.1) Focal adhesion
2) Extension via lamellipodia
3) Adhesion
4) Translocation
5) De-ashesion - 72What is it important to consider when comparing cell movement in the body vs what is study?When being studied cells are on a 2D structure, in the body they are in a 3D network
- 73What can happen to cells which migrate on cell surface? Why is the ECM therefore important?1) Can lead to detachment and apoptosis
2) Vital for cell adhesion - 74What directs the cell in migration? Especially in developmentCell adhesion molecules
- 75What are the key steps of leukocyte extravasation? What is the purpose of this?1) Chemoattraction
2) Rolling adhesion
3) Tight adhesion
4) Endothelial transmigration
Take immune cells from vascular system into the ECM - 76What happens in cell migration in cancer?1) Cleavage of cell-adhesion molecules (tumor become friable; cells can break off). Loosening of cell contacts helps migration, either as individual cells or groups (cells not held as firmly in ECM)
2) Cancer cells produce proteases etc which can degrade the ECM (or it can just turnover) which allows invasive cells to migrate and invade surrounding tissue and vasculature. - 77What happens when the ECM is degraded when cancer cell migrates?Leads to the release of ECM held growth factors and cytokines - this leads to increased growth and metastasis
- 78What happens when epithelial cells change to mesenchymal cells?Transcription factors secreted.
- 79What two things have to occur for cancer metastasis to occur?1) Loss of cell adhesion
2) Loss of apoptosis