Population Consequences of Single-Cell Damage Dynamics: Theory and Experiment under Glucose Limitation in E. coli

Microbial population growth arises from the survival and division of individual cells. However, under environmental stress, how reduced population fitness emerges from the single-cell dynamics remains poorly understood. Cellular aging and damage accumulation are often overlooked in linking these levels. Here, we use both theory and experiment to investigate how stochastic and asymmetric damage dynamics shape population outcomes. Theoretically, we apply a jump-diffusion damage model within a structured population framework to explore the roles of damage rate, noise, and partitioning asymmetry. Our theoretical analyses show that these parameters influence population growth both at equilibrium and during transient dynamics, suggesting that their cellular regulation may be a key strategy for sustaining population fitness. Experimentally, we expose Escherichia coli to glucose limitation and monitor stress responses using a RpoS fluorescent reporter, tracking both single-cell behavior in a microfluidic device combined with time-lapse fluorescence microscopy and population growth in a plate reader. Glucose limitation leads to the effects of elevated stress, reduced division, and increased mortality, which are consistently observed across scales. Using parameter estimates from single-cell data, our model deepens insights on population-level dynamics and highlights damage-noise driven, damage-dependent mortality as a key factor under stress. Together, these findings establish a quantitative framework linking intracellular stress to population fitness under environmental stress.