Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.
J Chem Phys. 2019 Dec 7;151(21):215103. doi: 10.1063/1.5127852.
Recently, we have reported that higher concentrations of dimethyl sulfoxide (DMSO) exhibit an enhancement in the structural ordering of the homogeneous N-palmitoyl-sphingomyelin (PSM) bilayer, whereas the presence of DMSO at lower concentrations leads to minor destabilization of the PSM bilayer structure. In this study, we aim to understand how these two modes of action of DMSO diversify for heterogeneous bilayers by employing atomistic molecular dynamic simulations. A binary bilayer system comprising PSM and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and a ternary bilayer system consisting of cholesterol along with PSM and POPC are the two heterogeneous biomimetic bilayers studied herein. We have simulated both the mixed lipid bilayer systems at 323 K, which is above the main phase transition temperature of the PSM lipid. This study reveals that DMSO exerts contrasting effects on the structure and stability of mixed bilayer systems, depending on its concentration. At 5 mol% of DMSO, the binary bilayer system shows slight disordering of lipid tails in conjunction with an appreciable increase in the area per lipid (APL), whereas for the ternary bilayer system, the orientational ordering of the lipid tails does not alter much; however, a slight expansion in the APL is observed. On the other hand, at 20 mol% of DMSO, an appreciable increase in the ordering of lipid tails for both the mixed bilayer systems occurs, depicting an enhancement in the structural stability of the bilayers. Furthermore, the H-bond analysis reveals that water-lipid H-bonding interaction decreases with increasing concentration of DMSO. We also observe contraction of the water-lipid interfacial region, pointing out DMSO induced dehydration at the lipid head-group region, and the dehydration effect is prominent for 20 mol% of DMSO. Furthermore, the computed free energies suggest that the free energy required for the transfer of a DMSO molecule from the lipid head-group region to the lipid head-tail interface is higher for the cholesterol containing ternary bilayer.
最近，我们已经报道称，较高浓度的二甲基亚砜（DMSO）会增强均相 N-棕榈酰鞘氨醇（PSM）双层的结构有序性，而在较低浓度下存在 DMSO 则会导致 PSM 双层结构的轻微失稳。在这项研究中，我们旨在通过原子分子动力学模拟来了解 DMSO 的这两种作用模式如何使非均相双层多样化。我们研究了两种非均相仿生双层，一种是由 PSM 和 1-棕榈酰-2-油酰基-sn-甘油-3-磷酸胆碱（POPC）组成的二元双层系统，另一种是由胆固醇与 PSM 和 POPC 组成的三元双层系统。我们在 323 K 下模拟了这两种混合脂质双层系统，该温度高于 PSM 脂质的主相变温度。这项研究表明，DMSO 对混合双层系统的结构和稳定性会产生相反的影响，这取决于其浓度。在 5 mol%的 DMSO 下，二元双层系统显示脂质尾部略微无序化，同时脂质面积（APL）显著增加，而对于三元双层系统，脂质尾部的取向有序性变化不大，但是 APL 略有增加。另一方面，在 20 mol%的 DMSO 下，两种混合双层系统的脂质尾部有序性都显著增加，表明双层的结构稳定性增强。此外，氢键分析表明，随着 DMSO 浓度的增加，水-脂质氢键相互作用减少。我们还观察到水-脂质界面区域收缩，这表明 DMSO 诱导了脂质头部区域的脱水，并且脱水效应在 20 mol%的 DMSO 下更为明显。此外，计算得到的自由能表明，从脂质头部区域转移到脂质头部-尾部界面的 DMSO 分子所需的自由能对于含有胆固醇的三元双层更高。
