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In Silico Reconstitution of Actin-Based Motility

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Background: Cell Movement

3D view of the bead and shell produced by the comet simulation

3D view of the bead and shell pro­duced by the comet sim­u­la­tion

Cells in our body use act­in to move. Unlike the actin-myosin inter­ac­tion that pro­duces mus­cle move­ment, this kind of move­ment is on a much small­er scale—the scale of indi­vid­u­al cells—and allows, for exam­ple, neu­rons to migrate and wire up to the right part of the brain, and cells in our immune sys­tem to track down and engulf bac­te­ria. To achieve this move­ment, cells lay down act­in poly­mer net­works that pro­duce force.

The in vitro model system: Bead Motility

One pop­u­lar way to study how our cells use act­in net­works to pro­duce force and move is using a sim­pli­fied sys­tem—actin-based bead motil­i­ty—which recre­ates motil­i­ty in vit­ro. To do this, we coat a bead with pro­teins that nor­mal­ly tell the cell to poly­mer­ize act­in, then put the bead a solu­tion sim­i­lar to that inside of the cell, which caus­es an act­in net­work to build around the bead. Sur­pris­ing­ly, even when the bead is spher­i­cal­ly sym­met­ric, rather than just build­ing a sym­met­ric shell that gets big­ger and big­ger, the bead moves off, on a ‘comet tail’ of act­in.

The Bead-Motility Simulator

This bead motil­i­ty sim­u­la­tor (named ‘Comet’) helps us under­stand how this process works, by recre­at­ing the process in sil­i­co.  It’s a top-down mod­el, based on idea that the large-scale elas­tic behav­ior of the net­work is the key to motil­i­ty, rather than small-scale fil­a­ment effects.  Because it’s able, by sim­u­lat­ing the elas­tic behav­ior alone, not only to repro­duce the exper­i­men­tal obser­va­tions, but also to make new pre­dic­tions that turn out to hold in the exper­i­men­tal sys­tem, it shows how the elas­tic behav­ior of the act­in net­work works to pro­duce motil­i­ty.

Reference

In Sil­i­co Recon­sti­tu­tion of Actin-Based Sym­me­try Break­ing and Motil­i­ty. (2009) Dayel MJ, Akin O, Lan­dery­ou M, Risca V, Mogilner A, et al.  PLoS Biol 7(9):e1000201. doi:10.1371/journal.pbio.1000201 (Free open-access arti­cle)

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