title: Hybrid Lipids Inspired by Extremophiles and Eukaryotes Afford Serum-Stable Membranes with Low Leakage.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, 92093-0358, USA.
authors.forename: Takaoki
authors.initials: T
authors.lastname: Koyanagi
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, 92093-0358, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Cao
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, 92093-0358, USA.
authors.forename: Geoffray
authors.initials: G
authors.lastname: Leriche
authors.affiliation: Department of Chemistry and Biochemistry, San Diego State University, San Diego, California, 92182-1030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Onofrei
authors.affiliation: Department of Chemistry and Biochemistry, San Diego State University, San Diego, California, 92182-1030, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Holland
authors.affiliation: Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700, Fribourg, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Mayer
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, 48109-2110, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sept
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, 92093-0358, USA.
authors.forename: Jerry
authors.identifier: http://orcid.org/0000-0002-8423-7376
authors.initials: J
authors.lastname: Yang
mesh_terms: D001105:Archaea / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000737:chemistry; D056890:Eukaryota / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007477:Ions / Q000737:chemistry; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D056004:Molecular Dynamics Simulation; D044967:Serum / Q000737:chemistry*
chemical_list: D007477:Ions; D008055:Lipids; D008081:Liposomes; D002784:Cholesterol
keywords: archaea; biomembranes; cholesterol; hybrid lipids; liposomes