Researchers at UC Merced have successfully built tiny artificial cells that can keep time, mimicking the natural 24-hour cycles found in living organisms
These artificial cells create new ways to study the internal clocks that regulate essential biological processes such as sleep and metabolism.
The breakthrough was recently published in Nature Communications and was led by Professors Anand Bala Subramaniam (bioengineering) and Andy LiWang (chemistry and biochemistry).
A big part of this research is gaining a deeper understanding of circadian rhythms, the internal biological clocks that operate on a roughly 24-hour cycle. These rhythms are essential for maintaining daily patterns in everything from energy use to hormone production. But until now, it’s been challenging to study how these clocks remain so reliable, even in the noisy, unpredictable environment inside cells.
Building synthetic clocks
The research team turned to a stripped-down system to answer this question. They reconstructed the circadian clock of cyanobacteria, microorganisms with one of the simplest known clock systems, using artificial, cell-like compartments known as vesicles.
These vesicles were specifically designed to contain key clock proteins that drive rhythmic behaviour. One protein was tagged with a fluorescent marker so its activity could be easily tracked.
The results showed that the artificial cells glowed in a predictable 24-hour rhythm, maintaining this pattern for at least four days. This glow acted as a visible signal that the synthetic clocks were working. But when the number of clock proteins inside the vesicles was reduced or the vesicles themselves were made smaller, the regular rhythm stopped. The disruption of the rhythm followed a consistent, measurable pattern.
The role of protein concentration
To understand why this happened, the researchers developed a computational model of the system. The model showed that higher concentrations of clock proteins made the artificial clocks more robust, helping the vesicles maintain accurate timing even when the amount of protein varied slightly between them. This suggests that biological clocks may rely on having a certain threshold of proteins to function correctly.
The model also suggested that a separate component of the natural circadian system, one involved in regulating gene expression, does not play a significant role in maintaining time within individual cells. Instead, its main job seems to be keeping clocks synchronised across a group of cells, ensuring that the whole organism stays in sync.
Aiding future research
Another unexpected finding was that some clock proteins tended to stick to the inside walls of the vesicles. This means the total amount of protein needed for a working clock is higher than previously thought, since some of it becomes inactive. These insights show how small physical and chemical factors can have a significant impact on biological timekeeping.
The study opens the door to further exploration of circadian rhythms using minimal, controllable systems. By using synthetic biology to rebuild complex processes in simpler settings, scientists can isolate and study the core mechanics of life in new ways. This work not only advances our understanding of how cells tell time but also provides a new tool for studying biological clocks in different organisms.
Multiple grants, including a National Science Foundation CAREER award, National Institutes of Health funding, and an Army Research Office grant, supported the project. Additional support came from the NSF CREST Centre for Cellular and Biomolecular Machines at UC Merced.