Energetic constraints on growth across biological scales.

Growth requires the continuous conversion of environmental resources into biomass and usable energy. Despite the high energetic efficiency of oxidative phosphorylation, the ability of cells and organisms to expand metabolism during growth is constrained by multiple physical and physiological factors. Increasing evidence suggests that metabolic strategies during growth are shaped not solely by energetic efficiency but by a series of constraints operating across biological scales: environmental factors such as temperature and oxygen availability impose external limits on metabolic demand and supply. At the organismal level, transport networks constrain the distribution of oxygen and nutrients. Within cells, geometric scaling, membrane allocation limits, biosynthetic capacity, and proteome investment restrict oxidative metabolism. Finally, recent thermodynamic analyses suggest that these diverse constraints may converge on a more general limit on free energy dissipation by cells. Together, these perspectives support the view that energetic constraints not only limit growth but actively shape how growth is achieved across biological scales. Under such constraints, cells frequently adopt alternative metabolic strategies, mainly increased reliance on fermentative pathways. Integrating energetic constraints across scales provides a unified framework for understanding metabolic strategies during growth.