Design principles of biochemical oscillators

Nat Rev Mol Cell Biol. 2008 Dec;9(12):981-91. doi: 10.1038/nrm2530. Epub 2008 Oct 30.


Cellular rhythms are generated by complex interactions among genes, proteins and metabolites. They are used to control every aspect of cell physiology, from signalling, motility and development to growth, division and death. We consider specific examples of oscillatory processes and discuss four general requirements for biochemical oscillations: negative feedback, time delay, sufficient 'nonlinearity' of the reaction kinetics and proper balancing of the timescales of opposing chemical reactions. Positive feedback is one mechanism to delay the negative-feedback signal. Biological oscillators can be classified according to the topology of the positive- and negative-feedback loops in the underlying regulatory mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Clocks / physiology*
  • Circadian Rhythm / physiology*
  • Feedback, Physiological / physiology*
  • Kinetics
  • Models, Biological*
  • Signal Transduction*