Sharma V K, Srinivasan H, García Sakai V, Mitra S
ISIS Facility, Science and Technology Facilities Council, Rutherford Appleton Laboratory, Didcot OX11 0QX, United Kingdom.
Struct Dyn. 2020 Sep 22;7(5):051301. doi: 10.1063/4.0000030. eCollection 2020 Sep.
Cationic lipid membranes have recently attracted huge attention both from a fundamental point of view and due to their practical applications in drug delivery and gene therapy. The dynamical behavior of the lipids in the membrane is a key parameter controlling various physiological processes and drug release kinetics. Here, we review the dynamical and thermotropic phase behavior of an archetypal cationic lipid membrane, dioctadecyldimethylammonium bromide (DODAB), as studied using neutron scattering and molecular dynamics simulation techniques. DODAB membranes exhibit interesting phase behavior, specifically showing coagel, gel, and fluid phases in addition to a large hysteresis when comparing heating and cooling cycles. The dynamics of the lipid membrane is strongly dependent on the physical state of the bilayer. Lateral diffusion of the lipids is faster, by an order of magnitude, in the fluid phase than in the ordered phase. It is not only the characteristic times but also the nature of the segmental motions that differ between the ordered and fluid phases. The effect of different membrane active molecules including drugs, stimulants, gemini surfactants, and unsaturated lipids, on the dynamical and thermotropic phase behavior of the DODAB membrane, is also discussed here. Various interesting features such as induced synchronous ordering between polar head groups and tails, sub diffusive behavior, etc., are observed. The results shed light on the interaction between these additives and the membrane, which is found to be a complex interplay between the physical state of the membrane, charge, concentration, molecular architecture of the additives, and their location within the membrane.
阳离子脂质膜最近从基础研究角度以及在药物递送和基因治疗中的实际应用方面都引起了极大关注。膜中脂质的动力学行为是控制各种生理过程和药物释放动力学的关键参数。在此,我们综述了一种典型阳离子脂质膜——二辛基二甲基溴化铵(DODAB)的动力学和热致相行为,这是通过中子散射和分子动力学模拟技术进行研究的。DODAB膜表现出有趣的相行为,具体而言,除了在比较加热和冷却循环时存在较大滞后现象外,还呈现出凝聚凝胶相、凝胶相和流体相。脂质膜的动力学强烈依赖于双层的物理状态。脂质在流体相中的横向扩散速度比在有序相中快一个数量级。不仅特征时间不同,有序相和流体相之间链段运动的性质也不同。本文还讨论了包括药物、刺激剂、双子表面活性剂和不饱和脂质在内的不同膜活性分子对DODAB膜动力学和热致相行为的影响。观察到了各种有趣的特征,如极性头基团和尾部之间诱导的同步有序排列、亚扩散行为等。这些结果揭示了这些添加剂与膜之间的相互作用,发现这是膜的物理状态、电荷、浓度、添加剂的分子结构及其在膜内的位置之间的复杂相互作用。