Journal
NATURE CHEMISTRY
Volume 6, Issue 4, Pages 295-302Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEM.1869
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Funding
- National Science Foundation [CCF-0832824, CMMI-1266402]
- Bourns College of Engineering at the University of California at Riverside (UC)
- UC Regents Faculty Development Fellowship
- European Commission [248919]
- German Research Foundation Cluster of Excellence Nanosystems Initiative Munich
- Elite Network of Bayern
- Direct For Computer & Info Scie & Enginr
- Division of Computing and Communication Foundations [0832824, 1317694] Funding Source: National Science Foundation
- Div Of Civil, Mechanical, & Manufact Inn
- Directorate For Engineering [1266402] Funding Source: National Science Foundation
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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.
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