From hot to cold: dissecting lipidome adaptation in Mycoplasma mycoides and the Minimal Cell JCVI-Syn3B

Cell membranes insulate and mediate interactions between life and its environment, with lipids determining their properties and functions. However, the intricacies of how cells adjust their lipidome compositions to tune membrane properties remain relatively undefined. The complexity of most model organisms has made it challenging to characterize lipidomic adaptation. An ideal model system would be a relatively simple organism with a single membrane that can adapt to environmental changes, particularly temperature, which is known to affect membrane properties. To this end, we used quantitative shotgun lipidomics to analyze temperature adaptation in Mycoplasma mycoides and its minimal synthetic counterpart, JCVI-Syn3B. Comparing with lipidomes from eukaryotes and bacteria, we observed a universal logarithmic distribution of lipid abundances. Additionally, the extent of lipid remodeling needed for temperature adaptation appears relatively constrained, irrespective of lipidomic or organismal complexity. Through lipid features analysis, we demonstrate head group-specific acyl chain remodeling as characteristic of temperature-induced lipidome adaptation and its deficiency in Syn3B is associated with impaired homeoviscous adaptation. Temporal analysis uncovers a two-stage cold adaptation process: swift cholesterol and cardiolipin shifts followed by gradual acyl chain modifications. This work provides an in-depth analysis of lipidome adaptation in minimal cells, laying a foundation to probe the fundamental design principles of living membranes.