Bridging ribosomal synthesis to cell growth through the lens of kinetics

Abstract

Understanding prokaryotic cell growth requires a multiscale modeling framework from the kinetics perspective. The detailed kinetics pathway of ribosomes exhibits features beyond the scope of the classical Hopfield kinetics model. The complexity of the molecular responses to various nutrient conditions poses additional challenge to elucidate the cell growth. Herein, a kinetics framework is developed to bridge ribosomal synthesis to cell growth. For the ribosomal synthesis kinetics, the competitive binding between cognate and near-cognate tRNAs for ribosomes can be modulated by Mg2+. This results in distinct patterns of the speed – accuracy relation comprising “trade-off” and “competition” regimes. Furthermore, the cell growth rate is optimized by varying the characteristics of ribosomal synthesis through cellular responses to different nutrient conditions. In this scenario, cellular responses to nutrient conditions manifest by two quadratic scaling relations: one for nutrient flux versus cell mass, the other for ribosomal number versus growth rate. Both are in quantitative agreement with experimental measurements.