Supplemental information and Data for: Colloidal physics modeling reveals how per-ribosome productivity increases with growth rate in E. coli

Faster growing cells must synthesize proteins more quickly. Increased
ribosome abundance only partly accounts for increases in total protein
synthesis rates. The productivity of individual ribosomes must increase
too, almost doubling by an unknown mechanism. Prior models point to
diffusive transport as a limiting factor but surface a paradox: faster
growing cells are more crowded, yet crowding slows diffusion. We suspected
physical crowding, transport, and stoichiometry, considered together,
might reveal a more nuanced explanation. To investigate, we built a
first-principles physics-based model of E. coli cytoplasm in
which Brownian motion and diffusion arise directly from physical
interactions between individual molecules of finite size, density, and
physiological abundance. Using our microscopically-detailed model, we
predict that physical transport of individual ternary complexes accounts
for ~80% of translation elongation latency. We also find that volumetric
crowding increases at faster growth even as cytoplasmic mass density
remains relatively constant. Despite slowed diffusion, we predict that
improved proximity between ternary complexes and ribosomes wins out,
illustrating a simple physics-based mechanism for how individual
elongating ribosomes become more productive. We speculate how crowding
imposes a physical limit on growth rate and undergirds cellular behavior
more broadly. Unfitted colloidal-scale modeling offers systems biology a
complementary “physics engine” for exploring how cellular-scale behaviors
arise from physical transport and reactions among individual molecules.