lecture 10 Flashcards
what happens when cell migration goes wrong
metastatic cancer
how do cells move?
mesenchymal cell migration, amoeboid cell migration
what are both migrations driven by
lamellipodial protrusions at leading edge
what is diff b/w ameboid and mesenchymal
ameboid is less adhesive
how do cells bind to extracellular env.
integrin receptors / extracellular matrix
descibe mesenchymal migration
fibroblasts; adhesion, harder to move, stuck to environment
describe ameboid migration
immune cells; move quicker, slip through to chase down pathogens
2 main ways for cells to move
lamellipodia (high or low adhesion), blebbing migration
step 1 of cell moving
adhere to surface (integrin receptors)
step 2 of cell moving
flatten and spread (integrin, actomyosin)
step 3 of cell moving
become polarized (tell front from back; microtubules)
step 4 of cell moving
generate protrusions (actin filaments; facilitates polarization)
step 5 of cell moving
form new adhesions, release old ones (combo of all 3)
step 6 of cell moving
directionally migrate intracellular signaling
how are epithelial cells that line surface anchored to underlying matrix
integrin adhesions
what happens if you disrupt integrin adhesions
would wipe cells right off dermis
what is cell matrix adhesion mediated by
integrin receptors
what happens when u see fiber laying across cell
it’s bound by integrins entire length of filament
what are integrins
transmembrane heterodimers that link ECM to cytoskeleton
what is collagen
glue that holds tissue and organs together
what binds to collagen fiber
integrin receptors
on cytoplasmic face, what connects to adhesions
actomyosin filaments
what does this mean for contractility
as actomyosin force is applied, attached to integrin, so pulling force is gonna be applied to outside env. (ECM)
what does alpha subunit do
participates in adhesion; facilitates adheion strength
what does beta subunit do
connects complex to actin filaments inside cell
vinculin
force sensor that triggers signaling
what does actin bind to
vinculin, talin (connects everything to integrin)
what does this machinery represent
continuous mechanical connection from ECM (outside) to cytoskeleton (inside)
describe integrin activation
can be off or on
describe integrin at surface
active
what happens once integrin active
at cell surface, binds to matrix and talin
what happens through talin
binds to vinculin (adaptor protein that links integrin complex to actin filaments)
what happens when you get force/contractility
positive feedback loop, more integrins, more actomyosin filaments, bigger+stronger adhesions, more effective force
does this positive feedback loop happen in fibroblasts or immune cells
fibroblasts