Varying the position of phospholipid acyl chain unsaturation modulates hopanoid and sterol ordering

Nguyen, Ha Ngoc Anh; Sharp, Liam; Lyman, Edward; Saenz, James P.

doi:10.1016/j.bpj.2024.06.002

Cited by 2 publications

References 36 publications

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A tuneable minimal cell membrane reveals that two lipid species suffice for life

Justice,

Kiesel,

Safronova

et al. 2024

Nat Commun

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All cells are encapsulated by a lipid membrane that facilitates their interactions with the environment. How cells manage diverse mixtures of lipids, which dictate membrane property and function, is experimentally challenging to address. Here, we present an approach to tune and minimize membrane lipid composition in the bacterium Mycoplasma mycoides and its derived ‘minimal cell’ (JCVI-Syn3A), revealing that a two-component lipidome can support life. Systematic reintroduction of phospholipids with different features demonstrates that acyl chain diversity is more important for growth than head group diversity. By tuning lipid chirality, we explore the lipid divide between Archaea and the rest of life, showing that ancestral lipidomes could have been heterochiral. However, in these simple organisms, heterochirality leads to impaired cellular fitness. Thus, our approach offers a tunable minimal membrane system to explore the fundamental lipidomic requirements for life, thereby extending the concept of minimal life from the genome to the lipidome.

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A tuneable minimal cell membrane reveals that two lipid species suffice for life

Justice,

Kiesel,

Safronova

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

A tuneable minimal cell membrane reveals that two lipid species suffice for life

Justice,

Kiesel,

Safronova

et al. 2023

Preprint

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All cells are encapsulated by a lipid membrane which facilitates the interaction between life and its environment. The property and function of the cell membrane is critically dependent on its lipidome composition which can range from 10s to 100s of unique lipid structures. How life has evolved to exploit such diverse mixtures of lipids has been experimentally challenging to address. In this study, we introduce a simple approach to minimize and tune lipidome composition in Mycoplasma mycoides and the Minimal Cell (JCVI-Syn3A). By varying the lipid composition of the growth medium, and introducing unmodifiable diether phospholipids, we demonstrate that a lipidome composed of two lipids can support life. By systematically reintroducing phospholipid features, we show that acyl chain diversity is more critical for supporting growth than head group diversity. We also reveal significant effects of altering phospholipid chirality on membrane permeability, cellular robustness, and growth, demonstrating how subtle changes in lipid stereochemistry can have profound effects on cell fitness. Our approach to tune mycoplasma lipidome composition introduces a minimal living model membrane system to understand the design principles and the role of lipid complexity in bioengineering of cell membranes.

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Varying the position of phospholipid acyl chain unsaturation modulates hopanoid and sterol ordering

Cited by 2 publications

References 36 publications

A tuneable minimal cell membrane reveals that two lipid species suffice for life

A tuneable minimal cell membrane reveals that two lipid species suffice for life

A tuneable minimal cell membrane reveals that two lipid species suffice for life

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