4:3 Flashcards
what inside the cell can generate traction force
• Talin + actin works with myosin to generate traction force
what is traction force
(pulling force)
how can actin connect to nuclear envelope
protein such as nesprin, SUN
what does the nuclear lamina do
(intermediate filament, provides strength, maintains shape)
• Nuclear lamina interacts with chromoatin
what is the focal adhesion complex
talin + vinculin
3 ECM properties
- Size/Shape
- Protein Composition
- Stiffness
describe types of cells shape determines
o Differentiation capacity changes
o Small, round= tend to go fat,
o large pointy= more bone formation
describe types of cells topography determines
• Smooth, pitted (rough)
o Rough= bone
How did the experiment with mygenin demonstrate mechanotransduction that changes lineage
Myogenin = muscle marker
- higher myogenin > higher MEF2C= mygenic differenation
// • Removed parts of the pathway o Removed integrin= muscle markers not shown= not moving to muscle
how does intracellular force alter talin + vinculin
- Higher tension rate (pN) > pulls more + exposes more sites (cryptic binding sites)
how many cryptic sites on tali + vinculin and what for
o Talin: up to 9 sites for vinculin
o Vinculin: up to 3 sites for MAPK
how does shape, size + stiffness alter traction force
o Shape size: increase size= increase traction force
o Stiffness: stiffer gel= larger cell (more spreading) = larger traction force
• // soft = small traction force + less FACs
how does nuclear lamina relate to stiffness
- Higher level of nuclear lamina (lamina A)= higher tissue stiffness
describe lamina A production as mechanosensed
o Mechanosense higher stiffness , pathway says need more nuclear lamina // mRNA make more lamina A
• Soft matrix = lower connections thru integrin usually
o // relatively low lamin A expression
• But more traction force> more connections > higher expression of lamin A
what does yap tax control
how big tissue is
how does yap tax work
TRANSLOCATION
o Stiff ECM + Large cell (high traction force)= YAPTAZ move into nucleus (becomes transcriptionally active)
• Can make bone
o Soft ECM + small cell (low traction force)= YAPTAZ stay in cytoplasm
• Can be fat cell
how does MRTFa work
TRANSLOCATION
o In stiff= needs more fActin (to build more traction force)
• // MRTF releases G-actin (which can make actin), and MRTF moves into nucleus
• // MRTF in nucleas when stiffer
What is mechanomemory
• Memory of previous mechanotransduction/mechanosensation
o Cell in stiff environment moved to soft, what happens?
• Longer culture on stiff = higher YAP
• Osteogenic potential goes up the longer in stiff
what is durotaxis
• Durotaxis = mechanotaxis= sense stiffness differences
o Cells move to higher traction force= bc it stabilises FAC + actin
