Understanding the mechanics of circadian rhythms

Circadian rhythms and other molecular clocks are essential to our survival and found in all organisms on Earth. Yet despite their ubiquity, they are not fully understood.

Recently, research has shown circadian rhythms are affected by a cell’s mechanical environment, in addition to their links to gene and biochemical interactions. Kennedy et al. investigate that mechanical link further through theoretical modeling of those experimental observations.

“Circadian rhythms are excellent examples of biochemical oscillators that have been studied using dynamical systems theory for years, but very little is known about how mechanics interacts with biochemistry to regulate our internal clock,” said author Jordi Garcia-Ojalvo.

Building on their previous experiment of mechanical controls with mammalian cells, the researchers applied mathematical models and bifurcation theory to study the link between circadian oscillations and mechanical signals in the cells. Their results support the theory that the activity of the mechanosensors YAP/TAZ affects circadian rhythms by increasing the expression of the clock gene Bmal1. Additionally, the results suggest circadian rhythms only occur when those mechanosensors are in the right activity range.

“I’m most excited about the perspectives that our findings open in integrating mechanics and biochemistry, which are unavoidably interlinked in multicellular organisms, but which have been under-studied so far,” Garcia-Ojalvo said. “Eventually, it should help us cope with medical issues affecting our circadian clock, which is closely linked with our health state and with our response to drugs.”

The researchers hope to experimentally verify the findings as well as model tissue-specific cells to incorporate mechanical effects in biochemical models.

Source: “Parametric modeling of mechanical effects on circadian oscillators,” by Keith E. Kennedy, Juan F. Abenza, Leone Rossetti, Xavier Trepat, Pablo Villoslada, and Jordi Garcia-Ojalvo, Chaos (2024). The article can be accessed at https://doi.org/10.1063/5.0164829 .

This paper is part of the Nonlinear dynamics, synchronization and networks: Dedicated to Juergen Kurths’ 70th birthday Collection, learn more here .