title: 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.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ariel Aharon
authors.initials: AA
authors.lastname: Cohen
authors.forename: Tomer
authors.initials: T
authors.lastname: Kalisky
authors.forename: Avi
authors.initials: A
authors.lastname: Mayo
authors.forename: Naama
authors.initials: N
authors.lastname: Geva-Zatorsky
authors.forename: Tamar
authors.initials: T
authors.lastname: Danon
authors.forename: Irina
authors.initials: I
authors.lastname: Issaeva
authors.forename: Ronen Benjamine
authors.initials: RB
authors.lastname: Kopito
authors.forename: Natalie
authors.initials: N
authors.lastname: Perzov
authors.forename: Ron
authors.initials: R
authors.lastname: Milo
authors.forename: Alex
authors.initials: A
authors.lastname: Sigal
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D002138:Calibration; D002453:Cell Cycle; D006801:Humans; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013050:Spectrometry, Fluorescence
chemical_list: D011506:Proteins; D012333:RNA, Messenger