Liu Bin, Hoopes Matthew I, Karttunen Mikko
Department of Chemistry and Waterloo Institute for Nanotechnology, University of Waterloo , 200 University Avenue West, Waterloo, Ontario, Canada N2L 3G1.
J Phys Chem B. 2014 Oct 9;118(40):11723-37. doi: 10.1021/jp5050892. Epub 2014 Sep 26.
An atomistic-level understanding of cationic lipid monolayers is essential for development of gene delivery agents based on cationic micelle-like structures. We employ molecular dynamics (MD) simulations for a detailed atomistic study of lipid monolayers composed of both pure zwitterionic dipalmitoylphosphatidylcholine (DPPC) and a mixture of DPPC and cationic cetyltrimethylammonium bromide (CTAB) at the air/water interface. We aim to investigate how the composition of the DPPC/CTAB monolayers affects their structural and electrostatic properties in the liquid-expanded phase. By varying the molar fraction of CTAB, we found the cationic CTAB lipids have significant condensing effect on the DPPC/CTAB monolayers, i.e., at the same surface tension or surface pressure, monolayers with higher CTAB molar fraction have smaller area per lipid. The DPPC/CTAB monolayers are also able to achieve negative surface tension without introducing buckling into the monolayer structure. We also found the condensing effect is caused by the interplay between the cationic CTAB headgroups and the zwitterionic phosphatidylcholine (PC) headgroups which has electrostatic origin. With CTAB in its vicinity, the P-N vector of PC headgroups reorients from being parallel to the monolayer plane to a more vertical orientation. Moreover, detailed analysis of the structural properties of the monolayers, such as the density profile analysis, hydrogen bonding analysis, chain order parameter calculations, and radial distribution function calculations were also performed for better understanding of cationic DPPC/CTAB monolayers.
对阳离子脂质单分子层进行原子水平的理解对于基于阳离子胶束样结构的基因递送剂的开发至关重要。我们采用分子动力学（MD）模拟对由纯两性离子二棕榈酰磷脂酰胆碱（DPPC）以及DPPC与阳离子十六烷基三甲基溴化铵（CTAB）的混合物组成的脂质单分子层在空气/水界面进行详细的原子研究。我们旨在研究DPPC/CTAB单分子层的组成如何影响其在液体扩张相中的结构和静电性质。通过改变CTAB的摩尔分数，我们发现阳离子CTAB脂质对DPPC/CTAB单分子层具有显著的凝聚作用，即在相同的表面张力或表面压力下，CTAB摩尔分数较高的单分子层每脂质的面积较小。DPPC/CTAB单分子层还能够在不使单分子层结构产生屈曲的情况下实现负表面张力。我们还发现凝聚作用是由具有静电起源的阳离子CTAB头基与两性离子磷脂酰胆碱（PC）头基之间的相互作用引起的。在CTAB附近，PC头基的P-N向量从与单分子层平面平行重新定向为更垂直的方向。此外，还对单分子层的结构性质进行了详细分析，如密度分布分析、氢键分析、链序参数计算和径向分布函数计算，以更好地理解阳离子DPPC/CTAB单分子层。
