4: 1 Flashcards
define mechanotransduction
the molecular mechanism by which cells sense and respond to mechanical signals.
How does myocardial infarction demonstrate tissue mechanics
o Portion dies and replaced by collagen (blue)
o Tissue mechanics change, i.e. collagen makes cardio stiffer
3 types of molecules in the ECMs
- Proteoglycans and GAGs
- Fibrous proteins
- Glycoproteins
What is a GAG
- (sugarchain) unbranched polysaccharide chains
What are the four groups of GAG
1) Hyaluronan
2) Chondroitinsulfate
3) Dermatansulfate
4) Keratansulfate
What are some features of a GAG
- Too stiff to fold into globular structures & Strongly hydrophilic
o High volume relative to the mass - space filler (not flexible enough to fold into small)
o Form hydrated gels even at the low concentrations (can hold high amount of water)
What attaches to GAG and what is this combinatorial molecule called
proteins attached =proteoglycans
what is a proteoglycan
GAG (sugar/polysaccharide) with a protein covalently attached
What GAG cannot add a protein
hyaluronan
difference between proteoglycan + glycoprotein
Proteo= mostly sugar + small protein
Glycopro= - mostly protein + small sugar
name two Common Proteoglycans: both core protein but different side chain of GAG number
- Decorin <10 GAG chains
2. Aggrecan >100 GAG chains
describe aggrecan
- proteoglycan
- • 100 aggrecans non-covalently bound to a single hyaluronan
• found in cartilage
• = high compression load bearing
• i.e knee joint
What are the major component of ECM
Fibrous protein= collagen
Describe the structure of collagen
- Gly-X-Y - ⍺ chain (usually X: proline and Y: hydroxyproline)
- Three together= Triple-stranded helical rod (B)
- Small glycine - interior of the triple helix // compact rod tightly
how many genes coding for different collagen ⍺ chains + how many types of collagen
human genome contains 42 distinct genes coding for different collagen ⍺ chains but only ~40 types of collagen (as triple helices)
= • Lot of gene coding but less combination
Models of fibrillar collagen assmebly
amino acid sequence > a chain > triple helix > collagen molecule > collagen fibril > collagen fiber
what are the types of collagen + function
- Type I is by far the most common collagen of skin and bone
- 90% of your body: types I to IV
- Types IX and XII are called fibril- associated collagens
what force does collagen resist
TENSILE force
Name 2 glycoproteins
Fibronectin
Laminin
how many genes codes fibronectin + how many types
• 1 gene codes it, (50 kb) but 20 different types
How many, and what’s inside the domains of fibronectin
• 3 domains within the protein (12 type I, 2 type II, 15-17 type III)
2 types of fibronectin
A. Plasma Fibronectin (soluble)
B. Cellular Fibronectin (insoluble)
Tension sensing function of fribronectin
- Cells can pull fribronectin and stretch a little
- insoluble fibronectin assemble into fibrils only on the surface of cells with appropriate fibronectin-binding proteins, integrin (whereas collagen that can self- assemble into fibrils in a test tube)
- some type III fn unfold (when stretched) to expose cryptic binding sites that interact with other fb resulting fn filaments formation
what is basal laminin and major compnents
- Specialised type of ECM called basal lamina (basement membrane)
- Laminin and type IV collagen, nidogen, perelman, integrin
is laminin a glycoprotein
yes
describe structure + number of combinations of laminin
- Trimeric structure with alpha, beta, and gamma chains (3 chains)
- 16 combinations found in vivo
how to name laminin
•3 chains= If have alpha 1, gamma 1, beta 1 // = laminin111
what degrades the matrix
• Degradation by MMPs (matrix metaloproteases)
