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Force generation in the lamellipod of crawling cells

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If you have a question about this talk, please contact Dr G Moller.

Many cells spread on surfaces and crawl across them by extending an actin-rich lamellipod – a thin section at the perimeter of the cell that is typically several micrometres broad, but less than 200nm high. The precise mechanism by which propulsive force is generated within the lamellipod is unknown. One popular model posits that protrusion operates by a Brownian ratchet mechanism, as actin filaments polymerize behind the fluctuating cell membrane and support its forward motion. We propose, rather, 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 complex is activated by proximity to highly-curved membrane. As the filaments polymerize, they form a dense, glass-like gel and because longer filaments pack less efficiently than shorter ones, excluded volume effects cause the gel to expand. If some of the actin filaments are bound by adhesions to the surface, this expansion results in forward motion of the leading edge. By conducting stochastic simulations of this non-equilibrium process in the steady-state regime, we show that our model can reproduce the characteristic force-velocity relation of motile cells, as well as the retrograde flow of actin. Our model also suggests why actin is branched within lamellipodia, and provides a potential explanation for the characteristic lamellipod height.

This talk is part of the Theory of Condensed Matter series.

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