ABOVE: Tardigrades use chemical cues to help them survive extreme environments. © iStock, SciePro

Tardigrades have gone through a lot for the sake of science. Scientists have launched them into space, dunked them in sub-freezing water, and shot them out of a gun.1-3 They are not quite indestructible, but they are close.

These squishy water bears use a strategy called cryptobiosis to survive everything from extreme temperatures to drying out. When they encounter harsh conditions, they enter a dormant state where metabolic processes grind to a halt, and they curl up into a ball called a tun. With this defense mechanism, tardigrades are one of the only species able to live in the most inhospitable corners of the globe. 

While scientists observed tardigrades repeatedly surviving conditions that should have been fatal, they still couldn’t figure out how tardigrades knew when to form tuns and how those tuns kept them alive. A new study published in PLOS One reveals for the first time how tardigrades harness chemicals to endure some deathly environments.4 Their results shed new light on how reversible chemical modifications can turn on and off the microbes’ defensive state.

 “A common misconception when people think about tardigrades is that they are extremophiles,” said Derrick Kolling, a chemist at Marshall University and author of the study. “They're not. Some can live under pretty adverse conditions relative to other animals, but really, their forte is being extremotolerant.”

The idea for the study emerged when Kolling, who was interested in the chemical world of microbes, decided to put tardigrades in a machine that measured molecules with unpaired electrons, such as oxides. To his surprise, the tardigrades seemed to make these molecules, especially when they formed tuns. Many common stressors can also spur the production of similar oxides in various organisms, so Kolling wondered whether oxidized molecules may play a role in tun formation. 

To answer this, he partnered with Leslie Hicks, a chemist at the University of North Carolina at Chapel Hill and coauthor of the study. They decided to focus on one tardigrade species, Hypsibius exemplaris. The team members stood at microscopes for hours, painstakingly excavating tardigrades from the algae in which they grew. Then they subjected the tardigrades to a battery of extreme conditions. Some conditions were fatal, but others, such as freezing temperatures and high water pressures, resulted in the tardigrades forming tuns and surviving the ordeals.

The researchers were especially intrigued to see that when they submerged the tardigrades in hydrogen peroxide to mimic chemical stress, they rapidly formed tuns. In particular, the oxides seemed to trigger tun formation by modifying an amino acid called cysteine in the tardigrades’ proteins. When the researchers prevented cysteine oxidation using other chemicals, the tardigrades no longer curled up into tuns—not just in response to hydrogen peroxide, but also when frozen or in high water pressure, suggesting that oxidizing signals play a central role in protecting tardigrades against a variety of stressors.

Oxidation seemed to be an on-off switch for tun formation, Kolling said. In stressful environments, the cysteines oxidized and triggered the process of tun formation. When the environment returned to normal, the oxidized cysteines reverted to their initial states and the tardigrades unrolled from their tuns.

“It's a really clear demonstration that these residues are involved,” Kolling said.

The fact that tardigrades’ defenses could be triggered by toxic chemicals—a process called chemobiosis—hadn’t been compellingly shown in tardigrades before, according to Łukasz Kaczmarek, an ecologist at Adam Mickiewicz University who was not involved in this study. Kaczmarek thinks that the new study fills a crucial gap in scientists’ understanding of tardigrade resilience.

“Now we know that chemobiosis is a real response of tardigrades,” Kaczmarek said. But he emphasized that there is still much more to learn about cryptobiosis in general. “We know almost nothing,” he said. “We know that some molecules are involved in this process, but how do they work? We don't know.”

For starters, Kaczmarek noted that this study focused on one tardigrade species and a limited set of stressors; he wondered whether similar responses might be found in other tardigrade species or in response to other stressors. Kolling and Hicks’s team focused on this tardigrade species because it’s relatively easy to work with, but they are also interested in studying the role of oxidation in cryptobiosis across many other species of tardigrades and other organisms.

“This was a chemical investigation into a biological system, and I think in this niche, there's so much work to be done and important questions to be answered,” Kolling said.