The Non-Equilibrium Dynamics of Bacterial Growth: Unifying Physical and Biochemical Models

<p dir="ltr">Bacterial metabolic strategies and modes of growth are fundamentally linked to their physical form and available biochemical resources. In this thesis, I develop models and the ory for intra-generational growth dynamics of bacterial cells (Chapter 2), gene expression driven non-exponential growth (Chapter 3), dynamic allocation of metabolizable energy to drive optimal growth (Chapter 4), and whole-cell metabolic flux balances dependent on physical constraints (Chapter 5). Our single-cell level intra-generational growth model pre dicts observed super-exponential growth from the autocatalytic nature of ribosomes as well as from growth localized to a subsection of the cell envelope. We also predict how noise in intra-generational and inter-generational processes regulate variability in cell morphology and generation times, revealing quantitative strategies for cellular resource allocation and morphogenetic noise control in different growth conditions. By incorporating gene expres sion and proteomeallocation, we find that changes to ribosomeexpression primarily control dry mass growth rate, whereas envelope expression more strongly affects cell elongation rate. Fitting to single-cell experimental data reproduces convex, super-exponential, and linear modes of growth, demonstrating how envelope and ribosome expression schedules drive cell-cycle-specific behaviors. These findings offer insights into how bacterial cells dynamically regulate elongation rates within each generation. By optimizing allocation the energy flux for growth, we accurately capture experimentally observed dependencies of bacterial cell size on growth rate, superlinear scaling of metabolic rate with cell size, and predict nutrient-dependent trade-offs between energy expended for growth, division, and shape maintenance. Encompassing both the mechanical properties of the cell and under lying biochemical regulation, we can further describe bacterial growth control in dynamic conditions such as nutrient shifts and osmotic shocks. By taking a finer-grained approach of metabolic flux balances, we find that bacterial growth efficiency peaks precisely at the onset of acetate overflow metabolism, framing this metabolic switch as an optimal trade off between efficient use of imported nutrients and rapid growth. We also demonstrate that the empirically observed scaling laws relating cell size and shape to growth rate represent an evolutionarily tuned compromise and find that the maximum sustainable cell size is inversely related to the growth rate.</p>