Water is fundamental to life. For plants, many environmental stresses, including drought, salinity, and heat, ultimately converge on a single problem: cells lose access to usable water. Although scientists have long known that cells can sense osmotic stress and activate downstream signaling pathways, one fundamental question has remained unanswered: can cells directly sense water itself?
On May 27, 2026, a research team led by Associate Professor Xiaofeng Fang at 蜜桃app published a study in Nature titled “Cellular water potential sensing via biomolecular condensation.”The work reveals, for the first time, that plant cells can directly perceive changes in cellular water status. The study further shows how this sensing mechanism rewires RNA transport and protein translation to help plants survive environmental stress.
Nature also highlighted the work in a Research Briefing article titled “Troubled waters: a protein senses when cells are running dry.”
Can Cells “Feel” Water?
Traditionally, water has been viewed largely as the passive solvent of the cell. In reality, however, cellular water exists in different states. Some water molecules tightly surround proteins, forming so-called hydration layers, while other water molecules remain relatively free.
Environmental stresses that lower cellular water potential alter these hydration states and simultaneously trigger many secondary changes, such as cell shrinkage, increased molecular crowding, and ion concentration shifts. Because hydration layers around proteins are extremely difficult to monitor directly, whether cells can truly sense hydration changes has remained elusive.
The Fang laboratory has long studied how biomolecular condensates formed through phase separation help plants perceive, respond to, and remember environmental stress. Since interactions between biomolecules and water strongly influence phase separation, the researchers proposed a bold idea: perhaps cells can directly sense water potential through the physical process of biomolecular condensation itself.
Using Heavy Water to Probe Hydration
To test this idea, the researchers designed an elegant experimental strategy using heavy water (D?O). Compared with normal water (H?O), heavy water forms stronger water–water hydrogen bonds but weaker water–protein interactions. This allows researchers to selectively reduce protein hydration without dramatically changing cell volume or molecular crowding (Fig. 1A).
Using this approach, the team identified a previously uncharacterized nuclear protein named SAM8. Under normal conditions, SAM8 is evenly distributed within the nucleus. Remarkably, within minutes of heavy water treatment, SAM8 rapidly assembled into nuclear condensates (Fig. 1B). Similar condensation was also triggered by drought, salt stress, and hyperosmotic stress. Importantly, this process occurred independently of classical osmotic stress signaling pathways, suggesting that SAM8 may directly sense changes in cellular water potential itself.
Figure 1. SAM8 undergoes water-dependent condensation. (A) Illustration of the impact of D?O. (B) SAM8 forms condensation in cells on D?O treatment.
A Sensor Built on Hydration Layers
Further biophysical analyses revealed that SAM8 is highly hydrophilic and surrounded by an unusually thick hydration shell. The researchers found that a negatively charged intrinsically disordered region within SAM8 creates a local electric field that strongly attracts and retains water molecules.
When water is abundant, this highly hydrated state prevents SAM8 molecules from interacting with one another, keeping the protein diffuse in the nucleus. However, when water potential decreases, the hydration layer weakens, allowing intermolecular interactions to rapidly increase and trigger condensation.
These findings suggest that the hydration state surrounding proteins can itself function as a previously unrecognized “physical sensing layer” used by cells to monitor the environment.
Figure 2. SAM8 possesses a thick hydration layer. (A) The charge distribution of SAM8. (B) Illustration and measurement of the hydration layer of SAM8.
Reprogramming Gene Expression for Survival
Once condensed, SAM8 selectively recruits key RNA export factors, including members of the ALY family and EIF4A3, leading to widespread retention of messenger RNAs inside the nucleus (Fig. 3).
This process ultimately reshapes cellular translation programs: translation of growth-related mRNAs is suppressed, while translation of stress-responsive mRNAs is enhanced. In effect, plants switch into a “survival-first” mode that prioritizes stress resistance over growth.
Plants lacking SAM8, or carrying mutant forms unable to undergo phase separation, show impaired translational reprogramming and become far more sensitive to water-deficit stress. Thus, SAM8 acts not only as a molecular water sensor, but also as a key regulatory hub linking environmental changes to gene expression control.
Figure 3. A working model for SAM8.
Beyond Chemical Signaling
The significance of this study extends beyond the discovery of a new stress-response protein. More fundamentally, it introduces a new conceptual framework for understanding how cells sense their environment.
For decades, environmental sensing has largely been viewed through the classical paradigm of “stimulus–receptor–signaling pathway–gene expression.” This work suggests that cells may not always require elaborate signaling cascades. In some cases, the intrinsic physicochemical properties of biomolecules themselves may be sufficient to directly perceive environmental change.
In other words, life may sense the world not only through chemical signals, but also through physical states.
Heavy Water Biology: A New Frontier?
The study also highlights heavy water not merely as an experimental reagent, but as a powerful biophysical probe. The strategy opens new possibilities for investigating cellular hydration, biomolecular condensation, and environmental sensing mechanisms.
More broadly, the work hints that “heavy water biology” could emerge as a new direction for exploring the physicochemical foundations of life.
The study was led by Associate Professor Xiaofeng Fang at the School of Life Sciences, 蜜桃app. Postdoctoral researcher Yunhe Wang was the first author of the paper. The work was supported by the Ministry of Science and Technology of China, the National Natural Science Foundation of China, 蜜桃app, Westlake Laboratory, and other funding agencies.
Editors: Li Han, John Paul Grima
