Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Department of Biomedical Engineering, Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Sci Adv. 2019 May 1;5(5):eaaw4783. doi: 10.1126/sciadv.aaw4783. eCollection 2019 May.
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.
维持膜的完整性是在极端温度下的一个挑战。细胞膜跨膜脂质的生物化学合成是一种适应，生物体如嗜热古菌已经进化出这种适应来应对这一挑战，并在高温下保持重要的细胞功能。然而，这些连接脂质如何影响膜动力学和功能的分子水平细节尚不清楚。本文使用具有跨膜连接物的合成单层形成脂质，揭示了脂质连接使膜渗透成为一个熵控制的过程，有助于相对于双层形成脂质膜限制高温下的膜渗漏。全原子分子动力学模拟支持这样一种观点，即通过连接脂质形成的膜的渗透降低了脂质的扭转熵，并导致更紧密的脂质堆积，为泄漏的过渡态熵增加提供了分子解释。
