Department of Mechanical and Industrial Engineering , Louisiana State University , Baton Rouge , Louisiana 70803 , United States.
Department of Chemical and Materials Engineering , University of Kentucky , Lexington , Kentucky 40506 , United States.
J Phys Chem B. 2019 Oct 3;123(39):8247-8260. doi: 10.1021/acs.jpcb.9b05525. Epub 2019 Sep 19.
High resolution differential scanning calorimetry (DSC) and molecular dynamics (MD) simulations were used to investigate the effect of three lignin dimers on the gel to fluid phase transition in DPPC lipid bilayers. The goal of this research is to begin to understand the partitioning of model lignin dimers into lipid bilayers and its effects on the gel to fluid transition temperature (). The long-term objective is to establish structure-function relationships for well-defined lignin derivatives at biologically relevant surfaces. This work uses a newly synthesized guiacylglycerol guaiacol ester with a hydroxypropenyl (HOCH-) group resembling natural lignin (GG dimer), compared with a truncated GG dimer without the HOCH- and benzyl-modified GG dimers. The DSC results show that the dimer most like natural lignin (with a hydroxypropenyl tail) has log = 2.72 ± 0.05, and MD simulations show that it associates with the headgroups of the lipid but does not penetrate strongly into the interior of the bilayer. Therefore, this dimer has little effect on the value. In contrast, the truncated dimer, which has been used as a representative GG dimer in prior studies, partitions into the bilayer, as seen in MD simulations, and shifts because of its increased lipophilicity (DSC log = 3.45 ± 0.20). Similarly, modification of the natural GG dimer by benzylation of the phenol makes it lipophilic (DSC log = 3.38 ± 0.28), causing it to partition into the bilayer, as seen in MD simulations and shift . In MD, we capture the transition from gel to fluid phase by defining and analyzing a normalized deuterium order parameter averaged over all carbon atoms located in the middle of the lipid tails. In this way, the phase transition can be clearly observed and, importantly, MD results show the same trend of transition temperature shifts as the DSC results. Furthermore, we compare partition coefficients estimated from free energy profiles calculated in MD to those obtained from experiment and they are in qualitative agreement. The success at predicting the structural effects of lignin dimers on lipid bilayers suggests that MD simulations can be used in the future to screen the interactions of lignin oligomers and their derivatives with lipid bilayers.
采用高分辨率差示扫描量热法（DSC）和分子动力学（MD）模拟研究了三种木质素二聚体对 DPPC 脂质双层从凝胶相到流态相转变的影响。本研究的目的是开始了解模型木质素二聚体在脂质双层中的分配及其对凝胶到流态转变温度（）的影响。长期目标是在生物相关表面上为明确定义的木质素衍生物建立结构-功能关系。这项工作使用了一种新合成的愈创木基甘油愈创木酚酯，带有类似于天然木质素的丙烯基（HOCH-）基团（GG 二聚体），与没有 HOCH-和苄基修饰的截断 GG 二聚体进行了比较。DSC 结果表明，最类似于天然木质素（带有丙烯基尾）的二聚体的 log = 2.72 ± 0.05，MD 模拟表明它与脂质的头基缔合，但不会强烈渗透到双层内部。因此，该二聚体对值的影响很小。相比之下，截断的二聚体在之前的研究中曾被用作代表性的 GG 二聚体，在 MD 模拟中观察到它分配到双层中，并且由于疏水性增加而导致 shift （DSC log = 3.45 ± 0.20）。同样，通过苯甲酰化酚修饰天然 GG 二聚体使其具有疏水性（DSC log = 3.38 ± 0.28），这导致它在 MD 模拟中分配到双层中，并 shift 。在 MD 中，我们通过定义并分析位于脂质尾部中间的所有碳原子的归一化氘序参数来捕捉从凝胶相到流态相的转变。通过这种方式，可以清楚地观察到相变，重要的是，MD 结果显示与 DSC 结果相同的转变温度 shift 趋势。此外，我们将从 MD 计算的自由能曲线中估算的分配系数与实验获得的分配系数进行了比较，它们在定性上是一致的。预测木质素二聚体对脂质双层结构影响的成功表明，MD 模拟可用于未来筛选木质素低聚物及其衍生物与脂质双层的相互作用。
