Nonequilibrium phase separation couples growth to chromosome segregation in Escherichia coli

The segregation of sister chromosomes is an essential step for cellular proliferation. Unlike eukaryotes, bacteria such as Escherichia coli lack cytoskeleton-based machinery to segregate their chromosomal DNA (nucleoids). Still, E. coli faithfully segregates nucleoids across a wide range of growth rates. Here, we provide theoretical and experimental evidence that nonequilibrium phase separation driven by polysome production promotes chromosome segregation and couples its timing to overall biomass growth across nutritional conditions. Polysome production inside the nucleoid, combined with polysome exclusion from the DNA meshwork, helps compact, split, segregate, and position nucleoids. Our continuum theoretical model predicts a linear relation between growth rate and normalized segregation time, which agrees with experiments. The theory also explains why halting chromosomal gene expression and thus polysome production immediately stops sister nucleoid migration, while ensuing polysome depletion gradually reverses nucleoid segregation. Furthermore, both theory and experiments show that redirecting gene expression away from the chromosome and toward plasmids causes ectopic polysome accumulations that are sufficient to drive aberrant nucleoid dynamics. Our findings suggest a robust self-organizing mechanism for coupling nucleoid segregation to cell growth.