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Molecular transport and packing underlie increasing ribosome productivity in faster growing cells

View ORCID ProfileAkshay J. Maheshwari, View ORCID ProfileEmma Gonzalez, View ORCID ProfileAlp M. Sunol, View ORCID ProfileDrew Endy, View ORCID ProfileRoseanna N. Zia
doi: https://doi.org/10.1101/2021.10.27.466129
Akshay J. Maheshwari
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
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Emma Gonzalez
2Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA
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Alp M. Sunol
2Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA
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Drew Endy
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
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  • For correspondence: endy@stanford.edu rzia@stanford.edu
Roseanna N. Zia
2Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA
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  • For correspondence: endy@stanford.edu rzia@stanford.edu
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Summary

Faster growing cells must make proteins more quickly. This occurs in part through increasing total ribosome abundance. However, the productivity of individual ribosomes also increases, almost doubling via an unknown mechanism. To investigate, we model both physical transport and chemical reactions among ensembles of individual molecules involved in translation elongation in Escherichia coli. We predict that the Damköhler number, the ratio of transport latency to reaction latency, for translation elongation is ~4; physical transport of individual ternary complexes accounts for ~80% of elongation latency. We also model how molecules pack closer together as growth quickens. Although denser cytoplasm both decreases transport distances and hinders motion, we predict that decreasing distance wins out, offering a simple mechanism for how individual elongating ribosomes become more productive as growth quickens. We also quantify how crowding imposes a physical limit on the performance of self-mixing molecular systems and likely undergirds cellular behavior more broadly.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 28, 2021.
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Molecular transport and packing underlie increasing ribosome productivity in faster growing cells
Akshay J. Maheshwari, Emma Gonzalez, Alp M. Sunol, Drew Endy, Roseanna N. Zia
bioRxiv 2021.10.27.466129; doi: https://doi.org/10.1101/2021.10.27.466129
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Molecular transport and packing underlie increasing ribosome productivity in faster growing cells
Akshay J. Maheshwari, Emma Gonzalez, Alp M. Sunol, Drew Endy, Roseanna N. Zia
bioRxiv 2021.10.27.466129; doi: https://doi.org/10.1101/2021.10.27.466129

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