page 889, Shemesh et al. suggest how formin builds actin filaments without tangling them. Formin, according to the new theory, slowly winds the filament and then undoes the twist with one big slip.
Formin caps the barbed ends of actin filaments, yet allows more monomers to be added. It has been proposed that a formin dimer works as if climbing stairs. The formin dimer initially contacts the terminal actin monomers but then releases its grip on the actin monomer second from the top, allowing it to bind a new actin monomer. When that new actin monomer is added, the free half of the formin dimer attaches to it. The other half of formin then releases its actin, and so on.
The model made sense but did not explain how torsion was accommodated. Each added actin monomer induces a slight rotation. As formin is often fixed in place at adhesion junctions, it cannot rotate. Actin filaments attached to both formin and the cytoskeleton cannot rotate freely either. Polymerization should thus induce torsional strain and cause supercoiling, but that is not seen. Now, the authors propose that formin periodically switches from stair stepping to a screw mode to release the accumulated strain.
A recent crystal structure revealed that formin dimers make a ring that hugs the barbed end like a screw cap, prompting the authors to imagine that the cap could turn either way. In their stair model, formin twists slightly in one direction (the shorter distance from monomer to monomer, ∼14°). But the cap might also turn the long way around (∼166°) in a screw-like mode if both halves of the formin dimer transiently release actin. The group modeled this theory using an elastic energy analysis.
The authors propose that torsional stress builds up with stair stepping until it is energetically favorable for formin to slip into screw mode. They estimate that every 12 steps should be followed by one screw mode slip. Although the prediction still awaits experimental verification, the regulation of polymerization mode by stress might apply to more than just actin.