Macroscopic Kinetic Effect of Cell-to-Cell Variation in Biochemical Reactions

TL;DR

This paper develops a theoretical framework to understand how cell-to-cell variation in enzyme levels influences the collective kinetics of biochemical reactions, revealing discrepancies between single-cell and population-level measurements.

Contribution

It introduces a novel model linking enzyme abundance variability to population-level reaction kinetics, challenging traditional Michaelis-Menten assumptions.

Findings

Population-level kinetics deviate from single-cell measurements.

Michaelis-Menten kinetics may be invalid at the population scale.

Cell-to-cell variation impacts observed metabolic reaction rates.

Abstract

Genetically identical cells under the same environmental conditions can show strong variations in protein copy numbers due to inherently stochastic events in individual cells. We here develop a theoretical framework to address how variations in enzyme abundance affect the collective kinetics of metabolic reactions observed within a population of cells. Kinetic parameters measured at the cell population level are shown to be systematically deviated from those of single cells, even within populations of homogeneous parameters. Because of these considerations, Michaelis-Menten kinetics can even be inappropriate to apply at the population level. Our findings elucidate a novel origin of discrepancy between in vivo and in vitro kinetics, and offer potential utility for analysis of single-cell metabolomic data.