Photochemical synthesis of natural membrane lipids in artificial and living cells

12 July 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

A general method for the abiogenesis of natural lipids could transform the development of lifelike artificial cells and unlock new ways to explore lipid functions in living cells. However, it is unclear if mild non-enzymatic methods can be harnessed to synthesize the diverse array of lipids found in biology. Here, we demonstrate the abiotic formation of natural lipids in water using visible-light-driven photoredox chemistry. Radical-mediated coupling of hydrocarbon tails to polar single-chain precursors yields lipids identical to those enzymatically formed. Spatiotemporally controlled lipid generation promotes de novo vesicle formation, growth, and division. Several photoredox catalysts, including those activated by nucleic acids, can drive lipid synthesis. Additionally, we show that the synthesis of bioactive lipids can trigger signaling in living cells.

Keywords

artificial cells
natural lipids
photoredox catalysis
RNA aptamer
biocompatible reaction

Supplementary materials

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Supplementary Materials
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This file contains: Materials and Methods; Supplementary Text; Figs. S1 to S26; Tables S1 to S3; Scheme S1 to S2 NMR spectra; References
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Movie S1
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POPC vesicle formation under green light over 30 min
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Movie S2
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control experiment in the absence of irradiation over 30 min
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Movie S3
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control experiment without eosin y under irradiation of green light over 30 min
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Movie S4
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in situ formed POPC vesicles growing under irradiation of green light over 15 min
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Movie S5
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in situ formed POPC vesicles continue to grow and undergo morphological changes under irradiation of green light over 15 min
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Movie S6
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in situ formed POPC vesicles in the absence of irradiation over 20 min
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