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REVIEW article

Front. Cell Dev. Biol.

Sec. Morphogenesis and Patterning

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1632969

This article is part of the Research TopicReconstitution Methods in Cell BiologyView all 4 articles

In vitro reconstitution of biological oscillators

Provisionally accepted
  • Molecular Systems Biology, Rijksuniversiteit Groningen, Groningen, Netherlands

The final, formatted version of the article will be published soon.

Oscillations are fundamental to biological timekeeping and organization, yet understanding how their complex temporal dynamics emerge from underlying molecular interactions remains a significant challenge. In vitro reconstitution offers a powerful bottom-up approach to dissect the minimal components, interactions, and parameters required to generate these rhythmic behaviors. Biochemical reconstruction of minimal oscillators outside of their native cellular contexts allows the direct interrogation of the biochemical, biophysical, and systems-level properties that govern oscillatory dynamics and unravel the governing fundamental design principles.In this review, we summarize the theoretical foundations of biological oscillators and outline the major experimental challenges associated with their in vitro reconstitution. We highlight recent advances in the reconstitution of diverse oscillator types, including the cyanobacterial circadian clock, the Min system from E. coli, and synthetic genetic oscillators such as the repressilator. These case studies illustrate how reconstitution efforts have yielded key mechanistic insights and driven technological innovation. We conclude by exploring emerging tools and future directions that promise to overcome current limitations and broaden the applicability of oscillator reconstitution -both to additional biological systems and to a wider range of scientific questions.

Keywords: Biological oscillators, In vitro reconstitution, Circadian clock, Min system, Synthetic Biology

Received: 21 May 2025; Accepted: 30 Jul 2025.

Copyright: © 2025 van der Vlist, de Vries and Kamenz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Julia Kamenz, Molecular Systems Biology, Rijksuniversiteit Groningen, Groningen, Netherlands

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