PT - JOURNAL ARTICLE AU - Kim, Young Hun AU - Leriche, Geoffray AU - Diraviyam, Karthik AU - Koyanagi, Takaoki AU - Gao, Kaifu AU - Onofrei, David AU - Patterson, Joseph AU - Guha, Anirvan AU - Gianneschi, Nathan AU - Holland, Gregory P. AU - Gilson, Michael K. AU - Mayer, Michael AU - Sept, David AU - Yang, Jerry TI - Entropic effects enable life at extreme temperatures AID - 10.1126/sciadv.aaw4783 DP - 2019 May 01 TA - Science Advances PG - eaaw4783 VI - 5 IP - 5 4099 - http://advances.sciencemag.org/content/5/5/eaaw4783.short 4100 - http://advances.sciencemag.org/content/5/5/eaaw4783.full SO - Sci Adv2019 May 01; 5 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.