Reconstructing the single-cell-level behavior of a toggle switch from population-level measurements

Tozaki, Hirokazu; Kobayashi, Tetsuya J.; Okano, Hiroyuki; Yamamoto, Ryo; Aihara, Kazuyuki; Kimura, Hidenori

doi:10.1016/j.febslet.2008.02.057

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Volume 582, Issue 7 , Pages 1067-1072, 2 April 2008

Reconstructing the single-cell-level behavior of a toggle switch from population-level measurements

Edited by Paul Bertone

Hirokazu Tozaki
- ERATO Aihara Complexity Modelling Project, JST, 45-18 Oyama, Shibuya-ku, Tokyo 151-0065, Japan
- Bio-Mimetic Control Research Center, The Institute of Physical and Chemical Research, RIKEN, 2271-130 Anagahora, Shimoshidami, Moriyama-ku, Nagoya, Aichi Prefecture 463-0003, Japan
- Corresponding authors, H. Tozaki for experiment and T.J. Kobayashi for theory.
Tetsuya J. Kobayashi
- Research Fellow of the Japan Society for the Promotion of Science, Japan
- Center for Developmental Biology, The Institute of Physical and Chemical Research, RIKEN, 2-2-3 Minatojima Minamimachi, Chuouku, Kobe-shi, Hyougo Prefecture 650-0047, Japan
- Corresponding authors, H. Tozaki for experiment and T.J. Kobayashi for theory.
Hiroyuki Okano
- Bio-Mimetic Control Research Center, The Institute of Physical and Chemical Research, RIKEN, 2271-130 Anagahora, Shimoshidami, Moriyama-ku, Nagoya, Aichi Prefecture 463-0003, Japan
Ryo Yamamoto
- Graduate school of Information Science and Technology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Kazuyuki Aihara
- ERATO Aihara Complexity Modelling Project, JST, 45-18 Oyama, Shibuya-ku, Tokyo 151-0065, Japan
- Graduate school of Information Science and Technology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Hidenori Kimura
- Bio-Mimetic Control Research Center, The Institute of Physical and Chemical Research, RIKEN, 2271-130 Anagahora, Shimoshidami, Moriyama-ku, Nagoya, Aichi Prefecture 463-0003, Japan
- Corresponding authors, H. Tozaki for experiment and T.J. Kobayashi for theory.

Received 15 October 2007; received in revised form 5 February 2008; accepted 22 February 2008. published online 04 March 2008.

Abstract

Single-cell-level behaviors of cells are typically inferred from ensemble measurements. However, such inferences implicitly assume a biological version of ergodicity: the percentage of cells in a state is identical to the probability to find a cell in that state. While the ergodicity does not always hold, it has been rarely tested. Here, we reveal that the ergodicity does not necessarily hold even for simple toggle switches and that apparent stabilities of the switches are due to a balance between single-cell-level biased stabilities and growth rates differences. Therefore, verification of the ergodicity and reconstructing single-cell-level behaviors are crucial for understanding intracellular systems.

Keywords: Intracellular switch, Stochastic flipping, Nonlinear master equation, Growth difference, Flow cytometry