Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona.
Janssen Research and Development, San Diego, California.
Biophys J. 2022 Nov 1;121(21):4205-4220. doi: 10.1016/j.bpj.2022.09.005. Epub 2022 Sep 9.
Phospholipid bilayers are liquid-crystalline materials whose intermolecular interactions at mesoscopic length scales have key roles in the emergence of membrane physical properties. Here we investigated the combined effects of phospholipid polar headgroups and acyl chains on biophysical functions of membranes with solid-state H NMR spectroscopy. We compared the structural and dynamic properties of phosphatidylethanolamine and phosphatidylcholine with perdeuterated acyl chains in the solid-ordered (s) and liquid-disordered (l) phases. Our analysis of spectral lineshapes of 1,2-diperdeuteriopalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE-d) and 1,2-diperdeuteriopalmitoyl-sn-glycero-3-phosphocholine (DPPC-d) in the s (gel) phase indicated an all-trans rotating chain structure for both lipids. Greater segmental order parameters (S) were observed in the l (liquid-crystalline) phase for DPPE-d than for DPPC-d membranes, while their mixtures had intermediate values irrespective of the deuterated lipid type. Our results suggest the S profiles of the acyl chains are governed by methylation of the headgroups and are averaged over the entire system. Variations in the acyl chain molecular dynamics were further investigated by spin-lattice (R) and quadrupolar-order relaxation (R) measurements. The two acyl-perdeuterated lipids showed distinct differences in relaxation behavior as a function of the order parameter. The R rates had a square-law dependence on S, implying collective mesoscopic dynamics, with a higher bending rigidity for DPPE-d than for DPPC-d lipids. Remodeling of lipid average and dynamic properties by methylation of the headgroups thus provides a mechanism to control the actions of peptides and proteins in biomembranes.
磷脂双层是液晶态物质，其介观尺度上的分子间相互作用在膜物理性质的出现中起着关键作用。在这里，我们使用固态 H NMR 光谱研究了磷脂极性头基团和酰基链对膜生物物理功能的综合影响。我们比较了具有氘代酰基链的磷脂酰乙醇胺和磷脂酰胆碱在固态有序（s）和液态无序（l）相中的结构和动态性质。我们对 1,2-二氘棕榈酰-sn-甘油-3-磷酸乙醇胺（DPPE-d）和 1,2-二氘棕榈酰-sn-甘油-3-磷酸胆碱（DPPC-d）在 s（凝胶）相中的谱线形状的分析表明，这两种脂质的链结构均为全反式旋转。与 DPPC-d 相比，DPPE-d 在 l（液晶）相中的片段有序参数（S）更高，而它们的混合物具有中间值，与氘代脂质类型无关。我们的结果表明，酰基链的 S 分布受头基团的甲基化控制，并在整个系统中平均化。通过自旋晶格（R）和四极有序松弛（R）测量进一步研究了酰基链分子动力学的变化。两种酰基-氘代脂质的弛豫行为随有序参数的变化表现出明显的差异。R 速率与 S 呈平方律关系，这意味着具有集体介观动力学的，DPPE-d 的弯曲刚性高于 DPPC-d 的脂质。通过头部基团的甲基化对脂质平均和动态性质的重塑，为控制肽和蛋白质在生物膜中的作用提供了一种机制。
