Metabolic heat flow from the minimal cell JCVI-Syn3B reveals the lipidome-dependence of growth and metabolism

Oertel, J.; Safronova, N.; Sáenz, J.; Fahmy, K. (2025) bioRxiv preprint. DOI: 10.1101/2025.09.12.675810

Summary

This collaborative study with Karim Fahmy’s group (HZDR) used isothermal microcalorimetry (IMC) to measure how lipidome composition affects heat dissipation — and by extension, metabolic efficiency — in JCVI-Syn3B cells. By extending the Monod equation into a calorimetric form, we quantified how seven defined lipid diets affect nutrient turnover, cell division rate, and biomass yield. Tuning lipidome composition produced considerable variations in energy dissipation relative to biomass production. Strikingly, maximal growth rate correlated with maximal lipid diversity, suggesting that the ability to tune local membrane charge and curvature through lipid structural diversity is crucial for divisome function.

Key Findings

• Lipidome composition causes surprisingly large variations in metabolic heat flow signatures of JCVI-Syn3B batch cultures.
• A calorimetric extension of the Monod equation was developed to extract growth rates and metabolic efficiency from IMC data.
• Cell volume becomes inversely coupled to lipidome-dependent entropic cost of cell division — cells on suboptimal lipid diets are larger and divide less efficiently.
• Maximal growth rate correlates with maximal lipid diversity, suggesting that lipid structural diversity is needed to support divisome function through local tuning of membrane charge and curvature.
• The trade-off between biomass yield and cell division rate depends systematically on lipid diet composition.

Methods

• Isothermal microcalorimetry (IMC): continuous measurement of heat dissipation during JCVI-Syn3B batch culture growth on 7 defined lipid diets.
• Calorimetric Monod equation: analytical framework relating heat flow to growth kinetics.
• Lipidomics and cell size measurements: combined with calorimetric data for per-cell analysis.

Significance

This paper introduced a new biophysical approach — metabolic calorimetry of minimal cells — to study how membrane composition influences cellular fitness. The correlation between lipid diversity and maximal growth rate provides the strongest evidence yet that lipidome complexity exists for a reason: it enables efficient cell division.