Hybrid Lipids Inspired by Extremophiles and Eukaryotes Afford Serum-Stable Membranes with Low Leakage.
- Koyanagi T Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, 92093-0358, USA.
- Cao KJ Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, 92093-0358, USA.
- Leriche G Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, 92093-0358, USA.
- Onofrei D Department of Chemistry and Biochemistry, San Diego State University, San Diego, California, 92182-1030, USA.
- Holland GP Department of Chemistry and Biochemistry, San Diego State University, San Diego, California, 92182-1030, USA.
- Mayer M Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700, Fribourg, Switzerland.
- Sept D Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, 48109-2110, USA.
- Yang J Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, 92093-0358, USA.
- 2017-04-04
Published in:
- Chemistry (Weinheim an der Bergstrasse, Germany). - 2017
archaea
biomembranes
cholesterol
hybrid lipids
liposomes
Archaea
Cell Line
Cholesterol
Eukaryota
Humans
Ions
Lipids
Liposomes
Microscopy, Fluorescence
Molecular Dynamics Simulation
Serum
English
This paper presents a new hybrid lipid that fuses the ideas of molecular tethering of lipid tails used by archaea and the integration of cholesterol groups used by eukaryotes, thereby leveraging two strategies employed by nature to increase lipid packing in membranes. Liposomes comprised of pure hybrid lipids exhibited a 5-30-fold decrease in membrane leakage of small ions and molecules compared to liposomes that used only one strategy (lipid tethering or cholesterol incorporation) to increase membrane integrity. Molecular dynamics simulations reveal that tethering of lipid tails and integration of cholesterol both reduce the disorder in lipid tails and time-dependent variance in area per lipid within a membrane, leading to tighter lipid packing. These hybrid lipid membranes have exceptional stability in serum, yet can support functional ion channels, can serve as a substrate for phospholipase enzymes, and can be used for liposomal delivery of molecules into living cells.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1002/chem.201701378
- PMID 28370726
- Persistent URL
- https://sonar.ch/global/documents/92920
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