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SUMMARY:Mechanisms of leading edge protrusion in interstitial migration - 
 Dr Guillaume Charras\, UCL\, London Centre for Nanotechnology 
DTSTART:20140228T140000Z
DTEND:20140228T150000Z
UID:TALK50332@talks.cam.ac.uk
CONTACT:Dr Eileen Nugent
DESCRIPTION:On two-dimensional substrates\, cells protrude by assembling a
  thin actin-rich veil at their leading edge. The molecular and biophysical
  mechanisms underlying formation of these protrusions are now well underst
 ood. However\, in physiology and pathophysiology\, cells migrate primarily
  in more complex three-dimensional environments: leukocytes migrate throug
 h a wide variety of tissues to combat inflammation and cancer cells leave 
 the primary tumour to metastasise. Despite relevance to immunity\, develop
 ment\, and cancer\, our understanding of the actin structures driving prot
 rusion in three-dimensional environments is poor. We studied chemotaxis of
  HL60 neutrophil-like cells through microfluidic channels with 5μmx5μm c
 ross-sections. In these interstices\, the leading edge of migrating cells 
 consisted of an actin-rich slab several microns thick filling the whole ch
 annel cross-section and composed of two distinct F-actin networks: an adhe
 rent network that polymerised perpendicular to cell-wall interfaces and a 
 free network that grew from the free membrane at the cell front. Photoblea
 ching experiments revealed that both networks interacted mechanically. Pol
 ymerisation of the free network was dependent upon the arp2/3 complex but 
 formation of the adherent network was not\, suggesting that each network r
 esulted from polymerisation by distinct nucleators. Removal of the free ne
 twork by arp2/3 inhibition led to a switch in mode of protrusion with the 
 formation of blebs at the leading edge but did not inhibit migration. Toge
 ther these data suggest a picture of cell migration in interstices where m
 edial growth of the adherent network prevents retrograde movement of the f
 ree network enabling new polymerisation to be converted into forward protr
 usion.
LOCATION:Small Lecture Theatre\, Cavendish Laboratory
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