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Phase Separation Induces Oscillations in Negative Feedback Loops
Alessandra Lucchetti1, Lukas H Kristensen1, Mogens H Jensen1
1University of Copenhagen, Niels Bohr Institute, Blegdamsvej 17, 2100 Copenhagen Ø, Denmark.
Physical Review Letters
|August 10, 2026
Summary
This study reveals how phase separation in cellular systems promotes oscillations by analyzing a minimal degradation-mediated negative feedback loop. These findings uncover a novel nonequilibrium mechanism for dynamic regulation in biological processes.
Area of Science:
- Biophysics
- Systems Biology
- Chemical Kinetics
Background:
- Oscillations are fundamental to nonequilibrium biological processes.
- Negative feedback loops are common regulatory mechanisms in cells.
- Degradation-mediated feedback involves the breakdown of molecular components.
Purpose of the Study:
- To analyze a minimal degradation-mediated negative feedback loop.
- To investigate the role of phase separation in promoting oscillations.
- To derive general criteria for oscillation onset in biological networks.
Main Methods:
- Coupling mean-field ordinary differential equations with phase-separated components.
- Analyzing linear enzymatic cascades with degradation.
- Developing a reduced time-delay model.
Main Results:
- Novel inhibition scalings were identified, expanding the parameter regime for oscillations.
- General bifurcation criteria were derived for arbitrary sublinear exponents and network sizes.
- Phase separation was shown to promote oscillations in the studied system.
Conclusions:
- Phase separation acts as a nonequilibrium mechanism for dynamic regulation in cellular systems.
- The study provides universal relations for oscillation onset.
- This work deepens the understanding of oscillatory dynamics in biology.
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