Protein Dynamics in Individual Human Cells: Experiment and Theory
Abstract
A current challenge in biology is to understand the dynamics of protein circuits in living human cells. Can one define and test equations for the dynamics and variability of a protein over time? Here, we address this experimentally and theoretically, by means of accurate time-resolved measurements of endogenously tagged proteins in individual human cells. As a model system, we choose three stable proteins displaying cell-cycle–dependant dynamics. We find that protein accumulation with time per cell is quadratic for proteins with long mRNA life times and approximately linear for a protein with short mRNA lifetime. Both behaviors correspond to a classical model of transcription and translation. A stochastic model, in which genes slowly switch between ON and OFF states, captures measured cell–cell variability. The data suggests, in accordance with the model, that switching to the gene ON state is exponentially distributed and that the cell–cell distribution of protein levels can be approximated by a Gamma distribution throughout the cell cycle. These results suggest that relatively simple models may describe protein dynamics in individual human cells.
Additional Information
© 2009 Cohen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: December 15, 2008; Accepted: January 20, 2009; Published: April 17, 2009. We thank the Kahn Family Foundation and the Israel Science Foundation for support. We thank Michael Elbaum and his lab for discussions and assistance with the calibration of fluorescence levels. Author Contributions: Conceived and designed the experiments: AAC TK AEM AS UA. Performed the experiments: AAC NGZ TD II NP. Analyzed the data: AAC TK AEM. Contributed reagents/materials/analysis tools: RBK RM AS. Wrote the paper: AAC TK AEM UA. The authors received funding from the Kahn Family Foundation and the Israel Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist.Attached Files
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Additional details
- PMCID
- PMC2668709
- Eprint ID
- 101341
- Resolver ID
- CaltechAUTHORS:20200218-151249080
- Kahn Family Foundation
- Israel Science Foundation
- Created
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2020-02-19Created from EPrint's datestamp field
- Updated
-
2023-06-01Created from EPrint's last_modified field