Department of Chemical Engineering, National Cheng Kung University, Tainan 70101, Taiwan.
Hierarchical Green-Energy Materials (Hi-GEM) Research Center, National Cheng Kung University, Tainan 70101, Taiwan.
Int J Mol Sci. 2019 Jul 2;20(13):3252. doi: 10.3390/ijms20133252.
Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic amphiphiles, is an inexpensive phospholipid substitute to fabricate vesicles with various pharmaceutical applications. Modulating the physicochemical and permeation properties of IPA vesicles are important for carrier designs. Here, we applied molecular dynamics simulations to examine the cholesterol effects on the structures, mechanics, and water permittivity of hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium- hexadecylsulfate (DTMA-HS) IPA bilayers. Structural and mechanical analyses indicate that both IPA systems are in gel phase at 298 K. Adding cholesterol induces alkyl chain ordering around the rigid sterol ring and increases the cavity density within the hydrophilic region of both IPA bilayers. Furthermore, the enhanced alkyl chain ordering and the membrane deformation energy induced by cholesterol increase the permeation free energy penalty. In contrast, cholesterol has minor effects on the water local diffusivities within IPA membranes. Overall, the cholesterol reduces the water permittivity of rigid IPA membranes due to the synergistic effects of increased alkyl chain ordering and enhanced membrane mechanical modulus. The results provide molecular insights into the effects of molecular packing and mechanical deformations on the water permittivity of biomimetic IPA membranes, which is critical for designing IPA vesicular carriers.
离子对两亲物（IPA）是由一对阳离子和阴离子两亲物组成的分子复合物，是一种廉价的磷脂替代品，可用于制备具有各种药物应用的囊泡。调节 IPA 囊泡的物理化学和渗透性质对于载体设计很重要。在这里，我们应用分子动力学模拟研究胆固醇对十六烷基三甲基铵-十二烷基硫酸盐（HTMA-DS）和十二烷基三甲基铵-十六烷基硫酸盐（DTMA-HS）IPA 双层结构、力学和水介电常数的影响。结构和力学分析表明，在 298 K 时，这两种 IPA 体系都处于凝胶相。添加胆固醇会导致刚性甾醇环周围的烷基链有序化，并增加两种 IPA 双层亲水区域内的腔密度。此外，胆固醇诱导的烷基链有序化和膜变形能增加了渗透自由能罚分。相比之下，胆固醇对 IPA 膜内水局部扩散系数的影响较小。总体而言，由于增加的烷基链有序化和增强的膜力学模量的协同作用，胆固醇降低了刚性 IPA 膜的水介电常数。这些结果为理解分子堆积和机械变形对仿生 IPA 膜水介电常数的影响提供了分子见解，这对于设计 IPA 囊泡载体至关重要。
