Physics-based colloidal-scale whole-cell model for Escherichia coli

In this work, we present a framework for physics-based whole-cell modeling of E. coli. Bacterial cells maintain cell fitness through cooperative organization and dynamics of biomolecules in response to environmental triggers. This cellular response is part of a physico-genetic expression-regulation cycle enacted by coordinating the spatiotemporal organization of proteins, ribosomes, and DNA across the entire cell. We build an efficient, colloidal-scale, dynamical whole-cell model with explicit representation of biomolecules to study protein/protein interactions that undergird this spatiotemporal regulation and environmentally triggered expression-regulation cycle. To enhance the resolution of our previous colloidal models, we develop a systematic refinement pipeline to map molecular and genomic details onto colloid surfaces. The resulting map yields a more detailed representation of the electrostatic, hydrophobic, and topographical features of the proteins and ribosomes for efficient large-scale modeling. To model the cellular DNA, we employ multi-scale, coarse-graining techniques to capture DNA structural features and its interaction with proteins. We characterize the effects of environmentally triggered proteomic response and the protein-protein interactions on the transport of translational molecules and gene expression.