Protein dynamics in individual human cells: Experiment and theory

Ariel Aharon Cohen, Tomer Kalisky, Avi Mayo, Naama Geva-Zatorsky, Tamar Danon, Irina Issaeva, Ronen Benjamine Kopito, Natalie Perzov, Ron Milo, Alex Sigal, Uri Alon

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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.

Original languageEnglish
Article numbere4901
JournalPLoS ONE
Issue number4
StatePublished - 17 Apr 2009
Externally publishedYes

Bibliographical note

Funding Information:
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.


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