BioControl:Week2/Notes

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I like to briefly notate every paper I read, and it made sense to put it here. feel free to add anything more -Kelsic Summary Eukaryotic Chemotaxis is locally dependent rather than globally polarized. Stochastic processes result in a biased-random-walk in the direction of chemical gradients: Membrane receptor binding events trigger local lamellipod extensions. Direction of chemical gradient determines an angular probability distribution for membrane extension. a single "compass-parameter" is sufficient to specify the probability distribution of the cell's biased random walk. dependent upon gradient strength and angular change per extension Experimental - Tracking cells during migration and chemotaxis: measured PI3-kinase activation in: primary DCs (I think this is Dendritic Cells) w/ C5a as a G protein coupled chemoattractant fibroblasts w/ platelet-derived growth factor (PDGF)as a tyrosine coupled chemoattractant Notes lamellipod extension seems to initial from mostly from the leading edge (which is another way of saying that the cell is polarized) chemotaxis is the biasing of the direction of movement for this leading edge the proposed "local coupling model" - receptor stimuli within the leading edge are coupled to unitary local lamellipod extensions that leads to a small turns to the right or left the unitary specification seems unnecessary as long as the coupling is local. assumptions - independent spatial signaling domains within the leading edge that are each capable of triggering local lamellipod extension. what could be the molecular mechanism of separation? diffusive or segregational? it seems that both are at work. scaling - typical local lamellipod extensions in DCs: leading edge: 20-30 micrometers local width, extension: micrometers time: 15-60 seconds local lamellipod extensions decouple left and right sides of leading edge, and each extension triggers a small turn in the direction of migration no significant temporal correlation between extensions on the right vs left side of leading edge slight correlation between mean extension (left vs right) and turn angle PI3K signaling PI3K concentration has cell polarization, and is activated by PDGF and C5a (PI3K indicated by Ph[Akt]-YFP tag ) membrane concentration used for normalization (indicated by CAAX-CFP tag) YFP/CFP indicates PI3K local stochastically initiated pulses 3-10 micrometers^2, 30-90s duration, initiated several times per minute rapid and transient local production, decay through diffusion and degredation 80% of PI3K pulses precide significant lamellipod extensions 20-40 seconds later significant correlation (~.15) of extension initiation within local region (+- ~6 micrometer) random migration in no gradient is a useful search strategy, which then naturally progresses to gradient-biased chemotaxis angular chemotaxis equation: P(a) = C*e(g/d)Cos(a) a - angle C - normalization constant d - angular step size. typically: 0.5-4. degrees g - gradient strength g/d - Compass parameter: completely specifies directional tendencies Background Wikipedia:Chemotaxis Wikipedia:Dendritic Cells Wikipedia:Fibroblasts Nature-Cell motility: Sharks' teeth and dunes - molecular lamellipod extension Purcell-Life at Low Reynolds Number - how cells move