A robust and tunable mitotic oscillator in artificial cells

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Abstract

Single-cell analysis is pivotal to deciphering complex phenomena like heterogeneity, bistability, and asynchronous oscillations, where a population ensemble cannot represent individual behaviors. Bulk cell-free systems, despite having unique advantages of manipulation and characterization of biochemical networks, lack the essential single-cell information to understand a class of out-of-steady-state dynamics including cell cycles. Here, by encapsulating Xenopus egg extracts in water-in-oil microemulsions, we developed artificial cells that are adjustable in sizes and periods, sustain mitotic oscillations for over 30 cycles, and function in forms from the simplest cytoplasmic-only to the more complicated ones involving nuclear dynamics, mimicking real cells. Such innate flexibility and robustness make it key to studying clock properties like tunability and stochasticity. Our results also highlight energy as an important regulator of cell cycles. We demonstrate a simple, powerful, and likely generalizable strategy of integrating strengths of single-cell approaches into conventional in vitro systems to study complex clock functions.

Data availability

The following data sets were generated

1. Guan Y
2. Li Z
3. Wang S
4. Barnes P
5. Liu X
6. Xu H
7. Jin M
8. Liu A
9. Yang Q
(2018) Data from: A robust and tunable mitotic oscillator in artificial cells
Available at Dryad Digital Repository under a CC0 Public Domain Dedication.

https://doi.org/10.5061/dryad.n8c8t

Article and author information

Author details

Ye Guan

Department of Biophysics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Zhengda Li

Department of Biophysics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Shiyuan Wang

Department of Biophysics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Patrick M Barnes

Department of Physics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Xuwen Liu

Department of Physics, University of Science and Technology of China, Hefei, China

Competing interests
The authors declare that no competing interests exist.
Haotian Xu

Department of Computer Science, Wayne State University, Detroit, United States

Competing interests
The authors declare that no competing interests exist.
Minjun Jin

Department of Biological Chemistry, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Allen P Liu

Department of Biophysics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0309-7018
Qiong Yang

Department of Biophysics, University of Michigan, Ann Arbor, United States

For correspondence
qiongy@umich.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2442-2094

Funding

National Institutes of Health (MIRA #GM119688)

Qiong Yang

National Science Foundation (CAREER Grant #1553031)

Qiong Yang

Alfred P. Sloan Foundation (Sloan Research Fellowship)

Qiong Yang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.