These tiny artificial cells can keep time like living creatures

According to new research from the University of California, Mercedes, tiny synthetic cells can keep time at amazing accuracy.

Using simplified, cellular-like structures, loading core clock proteins, scientists are able to mimic natural circadian rhythms that control everything from sleep cycles to metabolism. The study was published in Natural Communicationsprovides new insights on how the biological clock can remain so reliable, even in microscopic environments where molecular noise is prone to occur.

How to recreate a 24-hour rhythm in the minimum system

The research team led by bioengineer Anand Bala Subramaniam and biochemist Andy Liwang designed it as artificial cells, called vesicles, to accommodate key proteins behind the cyanobacterial circadian clock: Kaia, Kaib, and Kaic. By labeling a protein with fluorescent labels, they are able to track oscillations at luminous intensity every 24 hours.

“This study shows that we can use simplified synthetic systems to analyze and understand the core principles of biotiming,” Subramaniam said.

The light lasted for four days. However, the rhythm breaks when the protein concentration or vesicle size drops below the threshold. Failure follows a predictable pattern that proposes deeper rules.

Model clock fidelity across thousands of small cells

To explain what they saw, the team built a mathematical model that simulates clock behavior in thousands of vesicles with slightly different protein concentrations. This model reveals several key findings:

• High concentrations of clock protein are essential for reliable oscillation
• Smaller vesicles are unlikely to maintain rhythmic behavior
• Protein binding to membrane binding like KAIB reduces the number of proteins that can be used to run the clock
• A separate gene conversion loop helps synchronize the clock across populations, but each cell’s rhythm does not require

According to the results of Subramaniam and Liwang, natural cyanobacteria may overcome internal noise by maintaining high clock protein levels and using SASA and CIKA (such as SASA and CIKA). Their simulations showed that without these helper proteins, only about 86% of the simulated cells could maintain accurate time. Together with them, the number rose to 99.6%.

What this means for biology – Beyond

These findings go beyond bacteria. As Ohio State microbiologist Mingxu Fang pointed out, “This powerful tool can directly test organisms with different cell sizes may adopt different timing strategies.” The study’s combination of reconstructed biological parts and adjustable synthetic containers provides a general approach to studying complex biological behaviors in controlled settings.

Interestingly, the team also showed how clocks lose synchronization over time unless the gene expression feedback loop is active, just like keeping the band in directing in time. This suggests why even genetically identical cells may lose their rhythm if their molecular adjustments go out.

Looking to the future: Synthetic timing and system biology

Researchers at UC Merced University hope that eventually their approach can be expanded to build synthetic cells that not only maintain time, but also control gene expression with a circadian rhythm. This may open the door to more complex bioengineering systems and even new therapies for circadian-related diseases.

For now, this study highlights the simple fact that even the thinnest artificial cells can ticke like clockwork if you give them the right parts and enough space to move.

Magazine: Natural Communications
doi: 10.1038/S41467-025-61844-5

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