Maiti Archita, Daschakraborty Snehasis
Department of Chemistry, Indian Institute of Technology Patna, Patna, Bihar 801106, India.
J Phys Chem B. 2021 Feb 4;125(4):1167-1180. doi: 10.1021/acs.jpcb.0c08335. Epub 2021 Jan 22.
Extremophiles adopt strategies to deal with different environmental stresses, some of which are severely damaging to their cell membrane. To combat high osmotic stress, deep-sea organisms synthesize osmolytes, small polar organic molecules, like trimethylamine--oxide (TMAO), and incorporate them in the cell. TMAO is known to protect cells from high osmotic or hydrostatic pressure. Several experimental and simulation studies have revealed the roles of such osmolytes on stabilizing proteins. In contrast, the effect of osmolytes on the lipid membrane is poorly understood and broadly debated. A recent experiment has found strong evidence of the possible role of TMAO in stabilizing lipid membranes. Using the molecular dynamics (MD) simulation technique, we have demonstrated the effect of TMAO on two saturated fully hydrated lipid membranes in their fluid and gel phases. We have captured the impact of TMAO's concentration on the membrane's structural properties along with the fluid/gel phase transition temperatures. On increasing the concentration of TMAO, we see a substantial increase in the packing density of the membrane (estimated by area, thickness, and volume) and enhancement in the orientational order of lipid molecules. Having repulsive interaction with the lipid head group, the TMAO molecules are expelled away from the membrane surface, which induces dehydration of the lipid head groups, increasing the packing density. The addition of TMAO also increases the fluid/gel phase transition temperature of the membrane. All of these results are in close agreement with the experimental observations. This study, therefore, provides a molecular-level understanding of how TMAO can influence the cell membrane of deep-sea organisms and help in combating the osmotic stress condition.
极端微生物会采取策略来应对不同的环境压力，其中一些压力会严重损害它们的细胞膜。为了抵御高渗透压，深海生物会合成渗透调节物质，即小的极性有机分子，如氧化三甲胺（TMAO），并将其纳入细胞中。已知TMAO能保护细胞免受高渗透压或流体静压力的影响。多项实验和模拟研究揭示了此类渗透调节物质在稳定蛋白质方面的作用。相比之下，渗透调节物质对脂质膜的影响却知之甚少，且存在广泛争议。最近的一项实验发现了TMAO在稳定脂质膜方面可能发挥作用的有力证据。利用分子动力学（MD）模拟技术，我们证明了TMAO对处于流体相和凝胶相的两种饱和完全水合脂质膜的影响。我们捕捉到了TMAO浓度对膜结构性质以及流体/凝胶相转变温度的影响。随着TMAO浓度的增加，我们看到膜的堆积密度（通过面积、厚度和体积估算）大幅增加，脂质分子的取向有序性增强。由于与脂质头部基团存在排斥相互作用，TMAO分子被排斥在膜表面之外，这导致脂质头部基团脱水，从而增加了堆积密度。TMAO的添加还提高了膜的流体/凝胶相转变温度。所有这些结果都与实验观察结果密切吻合。因此，这项研究从分子层面解释了TMAO如何影响深海生物的细胞膜，并有助于应对渗透压胁迫条件。
