title: Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator.
abstract: In vitro compartmentalization of biochemical reaction networks is a crucial step towards engineering artificial cell-scale devices and systems. At this scale the dynamics of molecular systems becomes stochastic, which introduces several engineering challenges and opportunities. Here we study a programmable transcriptional oscillator system that is compartmentalized into microemulsion droplets with volumes between 33 fl and 16 pl. Simultaneous measurement of large populations of droplets reveals major variations in the amplitude, frequency and damping of the oscillations. Variability increases for smaller droplets and depends on the operating point of the oscillator. Rather than reflecting the stochastic kinetics of the chemical reaction network itself, the variability can be attributed to the statistical variation of reactant concentrations created during their partitioning into droplets. We anticipate that robustness to partitioning variability will be a critical challenge for engineering cell-scale systems, and that highly parallel time-series acquisition from microemulsion droplets will become a key tool for characterization of stochastic circuit function.
authors.affiliation: Systems Biophysics and Bionanotechnology, Physik Department and WSI/ZNN, Technische Universität München, 85748 Garching, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Weitz
authors.affiliation: Bioengineering, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Jongmin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Systems Biophysics and Bionanotechnology, Physik Department and WSI/ZNN, Technische Universität München, 85748 Garching, Germany.
authors.forename: Korbinian
authors.initials: K
authors.lastname: Kapsner
authors.affiliation: 1] Bioengineering, California Institute of Technology, Pasadena, California 91125, USA [2] Computation and Neural Systems, California Institute of Technology, Pasadena, California 91125, USA [3] Computer Science, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Winfree
authors.affiliation: Mechanical Engineering, University of California at Riverside, Riverside, California 92521, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Franco
authors.affiliation: Systems Biophysics and Bionanotechnology, Physik Department and WSI/ZNN, Technische Universität München, 85748 Garching, Germany.
authors.forename: Friedrich C
authors.identifier: 0000000338293446
authors.initials: FC
authors.lastname: Simmel
mesh_terms: D001671:Biochemistry; D004655:Emulsions; D008863:Microspheres; D016012:Poisson Distribution; D013050:Spectrometry, Fluorescence; D013269:Stochastic Processes; D014158:Transcription, Genetic
chemical_list: D004655:Emulsions