Reversible reaction shuts roundworms down

Freeze
© Neil Branda, Simon Fraser UniversityA nematode that has ingested a particular compound turns blue and stops in its tracks when exposed to ultraviolet light. The reaction is reversed with visible light and could provide a new tool for probing cell circuitry.
Scientists have stopped a tiny worm like a deer in the headlights, paralyzing it with a stream of light. The mechanism that induces the incapacitation isn't yet clear, but the paralysis occurs after the nematodes, C. elegans, are fed a molecule known to react to light. While toxic to some of the worms, the reaction appears to be reversible in others, researchers report online October 7 in the Journal of the American Chemical Society.

The work may add to the growing toolbox of molecules that biologists employ to study cells. By using light to trigger changes in molecules, scientists can spy on a cell's activity, witnessing what happens when messenger molecules speak with their target cells. "Light-driven reactions can be a powerful tool for studying biological processes," comments neuroscientist Ehud Isacoff of the University of California, Berkeley. Such approaches are already shedding light on the biochemistry underlying addiction, Parkinson's and other diseases in which brain circuitry goes awry.

Typical approaches "cage" a compound of interest, such as calcium, or tether it to a molecule that changes shape when energized by light. The shape change allows the compound to break out of the cage and do work, or to reach a target cell such as a nearby nerve. Though nothing was caged in this work, the molecule might be harnessed in such a way in the future.

In the case of the tiny, transparent C. elegans, the scientists don't know exactly how the compound paralyzed the worm, says study leader Neil Branda of Simon Fraser University in Burnaby, Canada. The team incubated the nematodes in dishes laced with a version of dithienylethene that is colorless and has an open ring at its center. When exposed to ultraviolet light, this center ring closes, altering the way the molecule's other parts stick out. After a few minutes of ultraviolet light, the worms that had eaten the open-ring version began to turn blue and showed signs of paralysis. In many of the worms, exposure to visible light reversed the paralysis and hue, though some worms died.

Worm
© Neil Branda, Simon Fraser UniversityWorms incubated with light-sensitive dithienylethene fluoresce after 10 minutes in ultraviolet light, establishing that the worms have taken in the shape-changing compound.
Because the worms are transparent, their blue hue revealed that the dithienylethene was undergoing the light-driven reaction that changed its shape and color. The closed-ring version of the compound is a better electron acceptor than the colorless open-ringed version, Branda notes. Perhaps the closed-ring form steals electrons that are key to a metabolic process, shutting down the worms. Visible light reopened the compound's center ring. Perhaps the open-ringed version doesn't intercept electrons and is a spectator, Branda speculates.

If the researchers can figure out what cells or molecules the dithienylethene interferes with and the mechanism of its action, the compound could be a useful probe and powerful tool, Isacoff says. "It's just begging for an explanation."