title: Cyclohexane Rings Reduce Membrane Permeability to Small Ions in Archaea-Inspired Tetraether Lipids.
abstract: Extremophile archaeal organisms overcome problems of membrane permeability by producing lipids with structural elements that putatively improve membrane integrity compared to lipids from other life forms. Herein, we describe a series of lipids that mimic some key structural features of archaeal lipids, such as: 1) single tethering of lipid tails to create fully transmembrane tetraether lipids and 2) the incorporation of small rings into these tethered segments. We found that membranes formed from pure tetraether lipids leaked small ions at a rate that was about two orders of magnitude slower than common bilayer-forming lipids. Incorporation of cyclopentane rings into the tetraether lipids did not affect membrane leakage, whereas a cyclohexane ring reduced leakage by an additional 40 %. These results show that mimicking certain structural features of natural archaeal lipids results in improved membrane integrity, which may help overcome limitations of many current lipid-based technologies.
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 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, CA, 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, CA, 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, CA, 92182-1030, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Holland
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mayer
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093-0358, USA. jerryyang@ucsd.edu.
authors.forename: Jerry
authors.identifier: http://orcid.org/0000-0002-8423-7376
authors.initials: J
authors.lastname: Yang
mesh_terms: D001105:Archaea / Q000737:chemistry*; D002463:Cell Membrane Permeability; D003510:Cyclohexanes / Q000737:chemistry*; D007477:Ions; D008055:Lipids / Q000737:chemistry*
chemical_list: D003510:Cyclohexanes; D007477:Ions; D008055:Lipids; C506365:Cyclohexane
keywords: Archaea; biomembranes; liposomes; permeability; self-assembly