EDITOR'S CHOICE IN DEVELOPMENTAL BIOLOGY
When a cell hits an obstacle, the actin filaments driving the membrane protrusion must reorganize and create additional branches to resist the pressure. Dan Fletcher at the University of California, Berkeley, and colleagues wanted to understand what effect that force has on the branching of actin filaments. They first glued unbranched actin filaments to a surface, some curved, some straight, and then added the raw materials necessary for the branching: the branch-initiating complex Arp2/3, the nucleation-promoting factor that activates it, and raw actin monomers, which polymerize into two tightly wound strands under the right conditions.
The researchers found that new actin branches were more likely to form on the convex side, or outer side, of curved segments. The questions were why and how the branching was occurring mostly on that side, says Fletcher. He recalled early studies on actin in which researchers noticed that isolated filaments would wiggle and squirm without the addition of any external energy. Though it was impossible to detect the wiggling at the scale of the isolated branching proteins under a microscope, Fletcher and colleagues wondered if the actin fragments they had immobilized still retained their wiggle, creating momentary curvature in certain areas and generating more branching. To test the idea, the team created a mathematical model to predict actin wiggling, and hypothesized that Arp2/3 would only bind when the curvature of the filament was greater than a certain value, and then imposed all the constraints of the experiment: the glue that held a filament down, the addition of Arp2/3, and the overabundance of raw actin proteins. The model fit.
When people think of mechanotransduction, they usually think of adhesion proteins, says Fletcher. But this study shows that “actin itself can be a sensor of its physical state,” and that the “structure that’s bearing the load may help organize the cell.” The results additionally hint at the possibility that some of the other 100 or so actin-binding proteins may also be regulated in part by the curvature of the strand. Curvature may turn out to be a “general mechanism for signaling during migration or other mechanotransduction processes,” says Harvard Medical School’s Jessica Tytell, who was not involved in the research.
V.I. Risca et al., “Actin filament curvature biases branching direction,” PNAS, 109:2913-18, 2012.