Genetically controlled membrane synthesis in liposomes

Nat Commun. 2020 Aug 28;11(1):4317. doi: 10.1038/s41467-020-17863-5.

Abstract

Lipid membranes, nucleic acids, proteins, and metabolism are essential for modern cellular life. Synthetic systems emulating the fundamental properties of living cells must therefore be built upon these functional elements. In this work, phospholipid-producing enzymes encoded in a synthetic minigenome are cell-free expressed within liposome compartments. The de novo synthesized metabolic pathway converts precursors into a variety of lipids, including the constituents of the parental liposome. Balanced production of phosphatidylethanolamine and phosphatidylglycerol is realized, owing to transcriptional regulation of the activity of specific genes combined with a metabolic feedback mechanism. Fluorescence-based methods are developed to image the synthesis and membrane incorporation of phosphatidylserine at the single liposome level. Our results provide experimental evidence for DNA-programmed membrane synthesis in a minimal cell model. Strategies are discussed to alleviate current limitations toward effective liposome growth and self-reproduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Liposomes / metabolism*
  • Membrane Lipids / biosynthesis*
  • Membrane Lipids / genetics*
  • Phosphatidylethanolamines / genetics
  • Phosphatidylethanolamines / metabolism
  • Phosphatidylglycerols / genetics
  • Phosphatidylglycerols / metabolism
  • Phospholipids / genetics
  • Phospholipids / metabolism
  • Proteomics

Substances

  • Liposomes
  • Membrane Lipids
  • Phosphatidylethanolamines
  • Phosphatidylglycerols
  • Phospholipids
  • phosphatidylethanolamine