UC Merced Study Shows Artificial Cells Keep 24-Hour Rhythm

Researchers at UC Merced, led by Professors Anand Bala Subramaniam and Andy LiWang, have demonstrated that synthetic vesicles, functioning as artificial cells, can maintain a consistent 24-hour fluorescent rhythm for at least four days, mimicking circadian rhythms observed in living organisms. The study, published in Nature Communications, involved loading these vesicles with core clock proteins, one of which was tagged with a fluorescent marker, and observing the rhythm was lost when protein numbers were reduced or vesicle size decreased. A computational model developed by the team indicated that higher concentrations of clock proteins enhance clock robustness, enabling reliable timekeeping despite protein variation, and that a gene-switching component, while crucial for population synchronisation, is not essential for individual clock maintenance.

The research revealed crucial principles about biological timekeeping through careful manipulation of their synthetic system. When the researchers reduced the number of clock proteins or shrunk the vesicle size, the rhythmic glow ceased in predictable patterns. Their computational model showed that higher concentrations of clock proteins create more robust timekeeping, enabling thousands of vesicles to maintain reliable rhythms even with slight variations in protein amounts. Interestingly, the team discovered that some clock proteins tend to adhere to vesicle walls, requiring high total protein counts to ensure proper function. The model also suggested that while certain components of natural circadian systems don’t significantly affect individual clocks, they’re essential for synchronizing timing across cell populations.

This innovative approach represents a major advance in circadian clock research methodology, as noted by Ohio State University microbiology professor Mingxu Fang, who praised the work’s ability to directly test how organisms with different cell sizes adopt distinct timing strategies. As Subramaniam explains, “This study shows that we can dissect and understand the core principles of biological timekeeping using simplified, synthetic systems.” The research, supported by National Science Foundation CAREER awards and grants from the National Institutes of Health and Army Research Office, provides a powerful new tool for understanding how life keeps time across different scales and organisms, potentially opening doors to new therapeutic approaches for circadian rhythm disorders.