How filament assembly dynamics can power the crawling motion of amoeboid cells

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• Dr Murray Stewart, MRC Laboratory of Molecular Biology, Cambridge
• Friday 16 February 2007, 14:15-15:15
• IRC in Superconductivity Seminar Room, Cavendish Laboratory.

If you have a question about this talk, please contact Dr Kalin Dragnevski.

Amoeboid cells crawl by extending a pseudopod at their leading edge while also drawing their trailing cell body forward. Both of these processes are driven by the polymerization dynamics of the cell cytoskeleton, which is composed of a meshwork of filaments that polymerize and depolymerise at defined locations in the cell. I will discuss results obtained from a simple and specialized model system that uses the sperm of the nematode Ascaris to investigate the mechanisms by which filament assembly dynamics can power cell locomotion. Although the nematode sperm system employs the protein MSP instead of the actin that forms the basis of motility in most other cells, its motile behaviour is very similar. Both protrusion and retraction can be reconstituted in vitro and these assays demonstrate that, whereas protrusion is driven by filament assembly, retraction involves filament disassembly. Although several models have been proposed to account for how polymerization drives protrusion, the precise mechanism remains controversial. I will present evidence that suggests that the way elongating filaments pack contributes substantially to this gel expansion. Tomography shows that filament packing in the nematode sperm motility machinery resembles that observed with rigid rods. Maximum rod packing density decreases dramatically as they lengthen. Thus as filaments elongate, the cytoskeleton gel must expand to accommodate their packing less densely. This volume expansion combines with polymerization to drive protrusion. Consistent with this hypothesis, an engineered MSP mutant that generates shorter filaments shows higher filament packing density and slower movement. Quantitation indicates that filament packing and polymerization contribute equally to the rate of protrusion in MSP fibres that produce the same pattern of movement as related actin-based systems. Actin filaments have similar stiffness and pack like MSP at the leading edge, indicating that gel expansion generated by filament packing effects would also contribute to protrusion in these systems.

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