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SUMMARY:Force generation in the lamellipod of crawling cells - Tom Duke\, 
 University College London
DTSTART:20101021T131500Z
DTEND:20101021T141500Z
UID:TALK26533@talks.cam.ac.uk
CONTACT:Dr G Moller
DESCRIPTION:Many cells spread on surfaces and crawl across them by extendi
 ng an actin-rich lamellipod – a thin section at the perimeter of the cel
 l that is typically several micrometres broad\, but less than 200nm high. 
 The precise mechanism by which propulsive force is generated within the la
 mellipod is unknown. One popular model posits that protrusion operates by 
 a Brownian ratchet mechanism\, as actin filaments polymerize behind the fl
 uctuating cell membrane and support its forward motion. We propose\, rathe
 r\, that excluded volume interactions between growing actin filaments are 
 a more significant cause of the propulsive force. In our model\, branched 
 actin filaments are nucleated at the leading edge\, where the Arp2/3 compl
 ex is activated by proximity to highly-curved membrane. As the filaments p
 olymerize\, they form a dense\, glass-like gel and because longer filament
 s pack less efficiently than shorter ones\, excluded volume effects cause 
 the gel to expand. If some of the actin filaments are bound by adhesions t
 o the surface\, this expansion results in forward motion of the leading ed
 ge. By conducting stochastic simulations of this non-equilibrium process i
 n the steady-state regime\, we show that our model can reproduce the chara
 cteristic force-velocity relation of motile cells\, as well as the retrogr
 ade flow of actin. Our model also suggests why actin is branched within la
 mellipodia\, and provides a potential explanation for the characteristic l
 amellipod height.
LOCATION:TCM Seminar Room\, Cavendish Laboratory
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