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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 20, 2017
- Source ID
- 10.1002/chem.201701378
Entities
People
- David Onofrei
- David Sept
- Geoffray Leriche
- Gregory P. Holland
- Jerry Yang
- Kevin J. Cao
- Michael Mayer
- Takaoki Koyanagi
Organizations
- Air Force Office of Scientific Research
- San Diego State University
- University of California, San Diego
- University of Fribourg
- University of Michigan