4D simulations of a minimal bacterial cell: An integration of theory and experiments

We present a whole-cell kinetic model (4D-WCM) of JCVI-syn3A, a minimal cell with a reduced genome of 493 genes that has retained few regulatory proteins or small RNAs. Cryo-electron tomograms provide the cell geometry and ribosome distributions, and from 3C maps an ensemble of DNA conformations. Time-dependent behaviors of concentrations and reaction fluxes from hybrid stochastic-deterministic simulations over a cell cycle reveal how the cell balances demands of its metabolism, genetic information processes, and growth, and offer insight into the principles of life for this minimal cell. Imaging of cells with labeled proteins and dyes reveal symmetric cell division, and on this basis we investigate the metabolic and genetic information processes accompanying growth and division. Using a newly developed polymer DNA model and treating the morphological changes in the membrane through a Helfrich Hamiltonian, we follow DNA replication, transcription, and translation processes over the cell cycle. The energy economy of each cellular process including active transport of amino acids, nucleosides, and ions is analyzed. Integration of experimental data and validation of the DNA polymer model by Martini/Gromacs MD simulations are critical steps in building the 4D-WCM model of a growing minimal bacterial cell.