Simple Growth–Metabolism Relations Are Revealed by Conserved Patterns of Heat Flow from Cultured Microorganisms

Abstract

Quantitative analyses of cell replication address the connection between metabolism and growth. Various growth models approximate time-dependent cell numbers in culture media, but physiological implications of the parametrizations are vague. In contrast, isothermal microcalorimetry (IMC) measures with unprecedented sensitivity the heat (enthalpy) release via chemical turnover in metabolizing cells. Hence, the metabolic activity can be studied independently of modeling the time-dependence of cell numbers. Unexpectedly, IMC traces of various origins exhibit conserved patterns when expressed in the enthalpy domain rather than the time domain, as exemplified by cultures of Lactococcus lactis (prokaryote), Trypanosoma congolese (protozoan) and non-growing Brassica napus (plant) cells. The data comply extraordinarily well with a dynamic Langmuir adsorption reaction model of nutrient uptake and catalytic turnover generalized here to the non-constancy of catalytic capacity. Formal relations to Michaelis–Menten kinetics and common analytical growth models are briefly discussed. The proposed formalism reproduces the “life span” of cultured microorganisms from exponential growth to metabolic decline by a succession of distinct metabolic phases following remarkably simple nutrient–metabolism relations. The analysis enables the development of advanced enzyme network models of unbalanced growth and has fundamental consequences for the derivation of toxicity measures and the transferability of metabolic activity data between laboratories.