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Bringing the genetically minimal cell to life on a computer in 4D
Zane R Thornburg1, Andrew Maytin2, Jiwoong Kwon3
1Beckman 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.
Cell
|March 10, 2026
Summary
We developed a 4D model of the JCVI-syn3A bacterium
Area of Science:
- Synthetic biology
- Computational biology
- Microbial cell biology
Background:
- The genetically minimal bacterium JCVI-syn3A has a short cell cycle (~100 min).
- Understanding its cell cycle dynamics requires integrated spatial and kinetic modeling.
Purpose of the Study:
- To create a comprehensive 4D whole-cell model of the JCVI-syn3A cell cycle.
- To simulate genetic, metabolic, growth, and division processes within the cell.
Main Methods:
- Integrated hybrid computational methods for 4D simulation (space and time).
- Brownian dynamics simulations for chromosome replication and segregation.
- Modeling growth based on lipid/membrane protein insertion, constrained by imaging data.
Main Results:
- The model accurately captures the origin-to-terminus ratio and other experimental data (doubling time, mRNA half-lives, protein distributions, ribosome counts).
- Simulations reveal stochasticity leading to unique daughter cells.
- Predicted average and heterogeneous partitioning to daughter cells.
Conclusions:
- The 4D whole-cell model provides a powerful tool for understanding minimal bacterial cell cycles.
- The model successfully integrates diverse cellular processes, from metabolism to division.
- It highlights the importance of stochasticity in generating cell-to-cell variability.
