Division of Physical Chemistry, Chemistry Department , Lund University , P.O. Box 124, 22100 Lund , Sweden.
Fachbereich Physik , Freie Universität Berlin , Arnimallee 14 , 14195 Berlin , Germany.
J Phys Chem B. 2018 Jun 28;122(25):6471-6482. doi: 10.1021/acs.jpcb.8b02159. Epub 2018 May 10.
Most land-living organisms regularly experience dehydration. In nature, one commonly applied strategy to protect against this osmotic stress is to introduce small polar molecules with low vapor pressure, commonly called osmolytes. Two examples of naturally occurring small polar compounds are urea and trimethylamine N-oxide (TMAO), which are known to have counteracting effects on protein stability. In this work, we investigate the effects of urea and TMAO on lipid self-assembly at varying water contents, focusing on dehydrated conditions. By using complementary experimental techniques, including sorption microcalorimetry, NMR, and X-ray scattering, together with molecular dynamics simulations in model systems composed of phosphatidylcholine lipids, water, and solute, we characterize interactions and self-assembly over a large range of hydration conditions. It is shown that urea and TMAO show qualitatively similar effects on lipid self-assembly at high water contents, whereas they have clearly different effects in dehydrated conditions. The latter can be explained by differences in the molecular interactions between the solutes and the lipid headgroups. TMAO is repelled from the bilayer interface, and it is thereby expelled from lipid lamellar systems with low water contents and narrow inter-bilayer regions. In these conditions, TMAO shows no effect on the lipid phase behavior. Urea, on the other hand, shows a slight affinity for the lipid headgroup layer, and it is present in the lipid lamellar system at all water contents. As a result, urea may exchange with water in dry conditions and thereby prevent dehydration-induced phase transitions. In nature, urea and TMAO are sometimes found together in the same organisms and it is possible that their combined effect is to both protect lipid membranes against dehydration and still avoid denaturation of proteins.
大多数陆生生物经常会经历脱水。在自然界中，一种常用的策略是引入低蒸汽压的小分子极性物质，通常称为渗透物。两种天然存在的小分子极性化合物是尿素和三甲胺 N-氧化物（TMAO），它们被认为对蛋白质稳定性有拮抗作用。在这项工作中，我们研究了尿素和 TMAO 在不同含水量下对脂质自组装的影响，重点研究了脱水条件。通过使用互补的实验技术，包括吸附微量热法、NMR 和 X 射线散射，以及由磷脂组成的模型体系中的分子动力学模拟，水和溶质，我们在广泛的水合条件下表征了相互作用和自组装。结果表明，尿素和 TMAO 在高含水量下对脂质自组装具有定性相似的影响，而在脱水条件下它们具有明显不同的影响。这可以用溶质与脂质头部基团之间的分子相互作用的差异来解释。TMAO 被排斥在双层界面之外，因此被排出含水量低和层间区域狭窄的脂质层状系统。在这些条件下，TMAO 对脂质相行为没有影响。另一方面，尿素对脂质头部基团层有轻微的亲和力，并且在所有含水量下都存在于脂质层状系统中。因此，尿素在干燥条件下可能与水交换，从而防止脱水诱导的相变。在自然界中，尿素和 TMAO 有时在同一生物体中同时存在，它们的联合作用可能是保护脂质膜免受脱水，同时避免蛋白质变性。
