BPS2026 – How do bacterial cells manage the membrane space?

The cytoplasmic membrane permits and controls the fluxes of material and energy to grow a bacterial cell. The essential activities harbored on the cytoplasmic membrane, such as transport, respiration, and secretion, are performed by the membrane proteins that comprise up to 10% of the total proteome in a bacterial cell. Recent quantitative data suggested that proteins could be almost packed on the cytoplasmic membrane, instead of being sparsely embedded or as “lipid rafts” that float around. Based on this picture, in this work, we experimentally test the membrane real-estate hypothesis the cytoplasmic membrane in bacteria is so packed with proteins that the cell needs to fine-tune the density, composition, and organization of the membrane proteins to optimize cell fitness. We show that the cytoplasmic membrane in E. coli is almost fully packed with proteins and their spatial localization can be systematically perturbed by overproducing of occupying components in single cells. The biosynthetic flux represented by the single-cell growth rate can be constrained by the abundance of the membrane proteome in a quantitative predictive manner. The nearly packed nature of membranes suggests a trade-off between the fitness benefit of maximizing the use of the surface area and the cost of overcrowding the membrane. Optimized density, composition, and organization of membrane proteins could be essential for improving cell fitness under different conditions, or for augmenting certain functions in engineered cells, possibly applicable to higher organisms.