Protein dynamics in individual human cells: experiment and theory

PLoS One. 2009;4(4):e4901. doi: 10.1371/journal.pone.0004901. Epub 2009 Apr 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calibration
  • Cell Cycle
  • Humans
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Messenger / genetics
  • Spectrometry, Fluorescence

Substances

  • Proteins
  • RNA, Messenger