Robust synchronization of the cell cycle and the circadian clock through bidirectional coupling

Area of Science:

• Cellular Biology
• Systems Biology
• Chronobiology

Background:

• The cell cycle and circadian clock are fundamental cellular rhythms.
• These rhythms are known to be coupled, with factors like BMAL1, Cyclin E, WEE1, CDK1, and REV-ERBα playing key roles.
• Previous models showed unidirectional coupling could entrain the cell cycle.

Purpose of the Study:

• To investigate the effects of bidirectional coupling between the cell cycle and circadian clock.
• To determine how coupling strength influences the synchronization of these two cellular rhythms.
• To explore the emergence of complex oscillations versus synchronized rhythms.

Main Methods:

• Merging detailed computational models of the cell cycle and circadian clock networks in mammalian cells.
• Analyzing the impact of unidirectional and bidirectional coupling on oscillation patterns.
• Varying coupling strengths to observe effects on synchronization and period length.

Main Results:

• Reverse unidirectional coupling (cell cycle to circadian clock) can entrain the circadian clock.
• Bidirectional coupling significantly reduces the occurrence of complex oscillations compared to unidirectional coupling.
• Synchronization of the cell cycle and circadian clock occurs readily under bidirectional coupling, often at intermediate periods, but also at periods outside the initial range.

Conclusions:

• Bidirectional coupling is crucial for robust synchronization of the cell cycle and circadian clock.
• Synchronization can manifest in simple periodic oscillations, birhythmicity, or trirhythmicity.
• The findings suggest that bidirectional coupling favors stable, synchronized cellular rhythms over complex, irregular oscillations.