Accounting for the plasticity and major drivers of minimal cellular metabolism

When model microbes like E. coli and S. cerevisiae grow fast, they coordinate their growth, metabolic rate, macromolecular makeup, and even morphology with remarkable precision. Such “growth laws” have inspired calibrated theoretical models of physiological adaptation, and also have enabled empirical predictions of cellular attributes. Yet, most of these patterns have been observed during relatively rapid growth or along stereotypical environmental perturbations, e.g. carbon limitation or sublethal antibiotic dosage. Does comparable coordination exist for cells that are not, or only slowly, growing? What processes set the scale of minimal cellular metabolism, and how plastic are such power requirements across cells and conditions? Towards answering these questions, we formulate simple biophysical estimates that bound the most relevant processes — including protein turnover, osmoregulation, and signal transduction — that likely dominate the energy budgets of non-growing cells. We give context to these estimates by building a census of empirical parameters and power densities of cells and organisms in diverse states of activity, unifying diverse data sources. These data include recent direct laboratory measurements of the power output of non-growing cells. Our analysis stresses the plasticity of basal power requirements across conditions; highlights persistent empirical mismatches between maintenance extrapolated at high growth and measured at low growth; and recommends specific experiments to resolve molecular processes enabled by cellular nonequilibrium.