Molecular transport and packing underlie increasing ribosome productivity in faster growing cells

Abstract

SummaryFaster growing cells must make proteins more quickly. This occurs in part through increasing total ribosome abundance. However, the productivity of individual ribosomes also increases, almost doubling via an unknown mechanism. To investigate, we model both physical transport and chemical reactions among ensembles of individual molecules involved in translation elongation in Escherichia coli. We predict that the Damköhler number, the ratio of transport latency to reaction latency, for translation elongation is ~4; physical transport of individual ternary complexes accounts for ~80% of elongation latency. We also model how molecules pack closer together as growth quickens. Although denser cytoplasm both decreases transport distances and hinders motion, we predict that decreasing distance wins out, offering a simple mechanism for how individual elongating ribosomes become more productive as growth quickens. We also quantify how crowding imposes a physical limit on the performance of self-mixing molecular systems and likely undergirds cellular behavior more broadly.