The findings could help make synthetic cells easier and cheaper to store and transport, for point-of-use production of medicines and other useful molecules
Study: Cytoplasmic abundant heat-soluble proteins from tardigrades protect synthetic Cells Under Stress (DOI: 10.1038/s41467-026-72328-5)
Key takeaways
- Researchers have shown how a tardigrade protein protects cell membranes, using the proteins to preserve synthetic cells that were dried out and rehydrated in the lab.
- The finding could lead to a way to store and transport "microfactories" for producing medicines and other biological products.
- Researchers at University of Michigan Engineering worked with the University of Chicago's Pritzker School of Molecular Engineering.
A protein found only in microscopic tardigrades, one that allows them to survive extreme conditions like dehydration, can convey similar durability in synthetic cells, according to new research from University of Michigan Engineering and the University of Chicago Pritzker School of Molecular Engineering.
The findings could reveal a new way to store and transport biological "microfactories." Constructed from cell building blocks like lipids, proteins and nucleic acids, the potential of synthetic cells includes producing medicines in less expensive facilities, delivering medicines to specific parts of the body, and detecting or consuming pollutants in the environment. However, they need to be kept cold when not in use.
"A major bottleneck in modern biotech is that many valuable biological products-things like vaccines, enzymes, cell-free reagents or biosensors-are fragile and require refrigeration or freezing during transport from factory to end-user," said Yongkang Xi, U-M research fellow in mechanical engineering and co-first author of the study published in Nature Communications. "This work shows a plausible way to change that."
The study, exploring how synthetic cells could come back from dehydration, was funded by the U.S. Army Research Office and the National Science Foundation.
Tardigrades, or "water bears" as they're often called, are among the most resilient creatures on Earth. When they become dehydrated, protective structures form within their cells to maintain structural integrity. The structures dissolve upon rehydration, allowing the cells to work again. In other animal cells, where this protein is not present, dehydration kills.
One such protein is called cytoplasmic abundant heat-soluble protein (CAHS12). Until now, researchers knew that it was important in preserving tardigrade cells under duress, but they didn't know exactly how it worked.
"What we found is that there are particular parts of the proteins that are really important for binding to the cell membrane and other parts that are involved in building the fibrous support system," said Andrew Ferguson, professor of molecular engineering at UChicago PME and co-corresponding author of the study. "We used molecular modeling to show why CAHS12 causes this protective behavior within synthetic cells and understand which parts of the protein lead to these properties."
Simulations showed that each CAHS12 protein has parts that are attracted to both the watery cell interior and the fat molecules of the cell membrane. In a hydrated cell, they float free, but as the cell dries out, the attraction to the membrane begins to dominate. The proteins, gathering and aligning near the membrane, trigger a chain reaction in which they link together, forming a 3D gel network that fills the cell. This stabilizes both the cell's surface and its delicate insides.
To see whether other cells could take advantage of the same proteins, U-M researchers created synthetic cells containing CAHS12 and subjected them to a dehydration-rehydration process. In this demonstration, the cells contained DNA that encoded a red fluorescent protein and the parts needed to turn those instructions into a red fluorescent signal.
After dehydrating and rehydrating the synthetic cells, the team then tested whether the internal machinery of the cell had survived-namely, had it retained the ability to read DNA and produce proteins? The synthetic cells glowed red under the microscope.
"What we see is that CAHS12 not only protects the membrane, but it also preserves the internal content, maintaining the biological activity," said Allen Liu, U-M professor of both mechanical and biomedical engineering and co-corresponding author of the study.
Key insights about how the proteins self-assembled came from computer simulations by co-first author Jianming Mao, a Ph.D. student in chemistry at UChicago. He used coarse-grained molecular dynamics to reveal the gel matrix that supported the cell through dehydration, answering questions about what happens to CAHS12 when it becomes dried out, how long it interacts with the cell membrane and what those interactions do.
This detailed information will help researchers design synthetic proteins that are specially designed to preserve biological materials, including synthetic cells, through dehydration. Then, when they arrive at the point of use, adding water brings them out of hibernation, just like a tardigrade.
