Cholesterol and POPC segmental order parameters in lipid membranes: solid state 1H-13C NMR and MD simulation studies
Cholesterol and POPC segmental order parameters in lipid membranes: solid state 1H-13C NMR and MD simulation studies
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DOI：
10.1039/c2cp42738a
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Topgaard, Daniel
中科院分区：
文献类型：
--
作者：
Ferreira, Tiago Mendes;Coreta-Gomes, Filipe;Topgaard, Daniel
细胞膜中胆固醇的浓度影响膜的流动性和厚度，并可能调节不同的过程，如脂筏的形成。由于解释生物膜的实验数据是相当复杂的，研究简单的模型与生物相关性是必要的，以了解自然系统。我们研究了胆固醇对由1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）组成的多层囊泡（MLV）分子结构的影响，POPC是一种在细胞膜中普遍存在的磷脂，其组成范围为0-60 mol%胆固醇。顺序参数，垂直酒吧S-CH垂直酒吧，实验确定通过使用H-1-C-13固态核磁共振（NMR）光谱与部分细节的所有部分的胆固醇和POPC分子，即环系统和烷基链的甾醇，以及甘油骨干，胆碱头基和SN-1和SN-2酰基链的POPC。随着胆固醇浓度的增加，酰基链逐渐采用更长的构象，而极性基团的取向和动力学不受影响。此外，我们进行经典的分子动力学模拟虚拟双层模仿POPC-胆固醇MLV的NMR研究。实验和模拟之间的良好协议被发现在双层中的胆固醇对齐和垂直酒吧S-CH垂直酒吧低于15摩尔%胆固醇的酰基链的配置文件。在胆固醇浓度较高时，POPC的胆碱头基和甘油主链部分以及磷脂和胆固醇烷基链发生偏差。前所未有的详细的NMR数据，使模拟和实验之间的更完整的比较POPC胆固醇双层，并可能有助于开发更现实的模型描述的生物膜。
The concentration of cholesterol in cell membranes affects membrane fluidity and thickness, and might regulate different processes such as the formation of lipid rafts. Since interpreting experimental data from biological membranes is rather intricate, investigations on simple models with biological relevance are necessary to understand the natural systems. We study the effect of cholesterol on the molecular structure of multi-lamellar vesicles (MLVs) composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a phospholipid ubiquitous in cell membranes, with compositions in the range 0-60 mol% cholesterol. Order parameters, vertical bar S-CH vertical bar, are experimentally determined by using H-1-C-13 solid-state nuclear magnetic resonance (NMR) spectroscopy with segmental detail for all parts of both the cholesterol and POPC molecules, namely the ring system and alkyl chain of the sterol, as well as the glycerol backbone, choline headgroup and the sn-1 and sn-2 acyl chains of POPC. With increasing cholesterol concentration the acyl chains gradually adopt a more extended conformation while the orientation and dynamics of the polar groups are rather unaffected. Additionally, we perform classical molecular dynamics simulations on virtual bilayers mimicking the POPC-cholesterol MLVs investigated by NMR. Good agreement between experiments and simulations is found for the cholesterol alignment in the bilayer and for the vertical bar S-CH vertical bar profiles of acyl chains below 15 mol% cholesterol. Deviations occur for the choline headgroup and glycerol backbone parts of POPC, as well as for the phospholipid and cholesterol alkyl chains at higher cholesterol concentrations. The unprecedented detail of the NMR data enables a more complete comparison between simulations and experiments on POPC-cholesterol bilayers and may aid in developing more realistic model descriptions of biological membranes.