Origins of Cell-to-Cell Bioprocessing Diversity and Implications of the Extracellular Environment Revealed at the Single-Cell Level
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Author(s)
Vasdekis, A. E.
Silverman, Andrew M.
Stephanopoulos, Gregory
Date Issued
December 2015
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Vasdekis, A. E., A. M. Silverman, and G. Stephanopoulos. “Origins of Cell-to-Cell Bioprocessing Diversity and Implications of the Extracellular Environment Revealed at the Single-Cell Level.” Scientific Reports 5 (December 14, 2015): 17689.
Version
Final published version
Abstract
Bioprocess limitations imposed by microbial cell-to-cell phenotypic diversity remain poorly understood. To address this, we investigated the origins of such culture diversity during lipid production and assessed the impact of the fermentation microenvironment. We measured the single-cell lipid production dynamics in a time-invariant microfluidic environment and discovered that production is not monotonic, but rather sporadic with time. To characterize this, we introduce bioprocessing noise and identify its epigenetic origins. We linked such intracellular production fluctuations with cell-to-cell productivity diversity in culture. This unmasked the phenotypic diversity amplification by the culture microenvironment, a critical parameter in strain engineering as well as metabolic disease treatment.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1038/srep17689
