BioControl:Week2/Notes

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Best of 2007-2008

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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:
    1. Membrane receptor binding events trigger local lamellipod extensions.
    2. 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

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