RT Journal Article SR Electronic T1 Entropic effects enable life at extreme temperatures JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eaaw4783 DO 10.1126/sciadv.aaw4783 VO 5 IS 5 A1 Kim, Young Hun A1 Leriche, Geoffray A1 Diraviyam, Karthik A1 Koyanagi, Takaoki A1 Gao, Kaifu A1 Onofrei, David A1 Patterson, Joseph A1 Guha, Anirvan A1 Gianneschi, Nathan A1 Holland, Gregory P. A1 Gilson, Michael K. A1 Mayer, Michael A1 Sept, David A1 Yang, Jerry YR 2019 UL http://advances.sciencemag.org/content/5/5/eaaw4783.abstract AB Maintaining membrane integrity is a challenge at extreme temperatures. Biochemical synthesis of membrane-spanning lipids is one adaptation that organisms such as thermophilic archaea have evolved to meet this challenge and preserve vital cellular function at high temperatures. The molecular-level details of how these tethered lipids affect membrane dynamics and function, however, remain unclear. Using synthetic monolayer-forming lipids with transmembrane tethers, here, we reveal that lipid tethering makes membrane permeation an entropically controlled process that helps to limit membrane leakage at elevated temperatures relative to bilayer-forming lipid membranes. All-atom molecular dynamics simulations support a view that permeation through membranes made of tethered lipids reduces the torsional entropy of the lipids and leads to tighter lipid packing, providing a molecular interpretation for the increased transition-state entropy of leakage.