Bringing the genetically minimal cell to life on a computer in 4D

Zane R Thornburg¹, Andrew Maytin², Jiwoong Kwon³, Troy A Brier⁴, Benjamin R Gilbert⁴, Enguang Fu⁵, Yang-Le Gao⁴, Jordan Quenneville⁴, Tianyu Wu⁶, Henry Li⁷, Talia Long⁴, Weria Pezeshkian⁸, Lijie Sun⁹, John I Glass⁹, Angad P Mehta¹⁰, Taekjip Ha¹¹, Zaida Luthey-Schulten¹²

Affiliations

¹ Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
² NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
³ Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁴ Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁵ Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA; NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA.
⁶ NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁷ NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA.
⁸ Niels Bohr International Academy, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark.
⁹ J. Craig Venter Institute, La Jolla, CA, USA.
¹⁰ Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA; NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹¹ Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA.
¹² Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA; NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address: zan@illinois.edu.

PMID: 41806832
DOI: 10.1016/j.cell.2026.02.009

Free article

Bringing the genetically minimal cell to life on a computer in 4D

Zane R Thornburg et al. Cell. 2026.

Free article

. 2026 Mar 9:S0092-8674(26)00174-1.

doi: 10.1016/j.cell.2026.02.009. Online ahead of print.

Authors

Affiliations

¹ Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
² NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
³ Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁴ Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁵ Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA; NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA.
⁶ NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁷ NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA.
⁸ Niels Bohr International Academy, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark.
⁹ J. Craig Venter Institute, La Jolla, CA, USA.
¹⁰ Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA; NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹¹ Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA.
¹² Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA; NSF Science and Technology Center for Quantitative Cell Biology, Urbana, IL, USA; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address: zan@illinois.edu.

PMID: 41806832
DOI: 10.1016/j.cell.2026.02.009

Abstract

We present a whole-cell spatial and kinetic model for the ∼100 min cell cycle of the genetically minimal bacterium JCVI-syn3A. We simulate the complete cell cycle in 4D (space and time), including all genetic information processes, metabolic networks, growth, and cell division. By integrating hybrid computational methods, we model the dynamics of morphological transformations. Growth is driven by insertion of lipids and membrane proteins and constrained by fluorescence imaging data. Chromosome replication and segregation are controlled by the essential structural maintenance of chromosome proteins, analogous to condensin (SMC) and topoisomerase proteins in Brownian dynamics simulations, with replication rates responding to deoxyribonucleotide triphosphate (dNTP) pools from metabolism. The model captures the origin-to-terminus ratio measured in our DNA sequencing and recovers other experimental measurements, such as doubling time, mRNA half-lives, protein distributions, and ribosome counts. Because of stochasticity, each replicate cell is unique. We predict not only the average behavior of partitioning to daughter cells but also the heterogeneity among them.

Keywords: DNA sequencing; Lattice Microbes; cell cycle; fluorescence imaging; minimal cell; whole-cell modeling.

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Declaration of interests The authors declare no competing interests.

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Bringing the genetically minimal cell to life on a computer in 4D

Affiliations

Bringing the genetically minimal cell to life on a computer in 4D

Authors

Affiliations

Abstract

Conflict of interest statement

LinkOut - more resources

Full Text Sources