Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
Chemical and Engineering Materials Division, Neutron Sciences Directorate, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.
Phys Chem Chem Phys. 2017 Jan 18;19(3):2514-2524. doi: 10.1039/c6cp06202d.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used medications in the world for their analgesic, antipyretic, and anti-inflammatory actions, despite a well-known incidence of a wide spectrum of their adverse effects. To a great extent, beneficial action and side effects of NSAIDs are associated with the interaction of these drugs at the cell membrane level. Here, we use neutron scattering to combine elastic intensity scans, quasielastic and neutron spin echo (NSE) measurements to understand the effect of aspirin, a commonly used NSAID, on the dynamical and phase behavior of the membrane of dimyristoylphosphatidylcholine (DMPC), a prominent representative of phospholipids residing in the outer leaflet of the human erythrocyte membrane. Elastic intensity scans reveal that addition of aspirin not only eliminates the pre-transition (solid gel to ripple phase), but also broadens the main phase transition (ripple to fluid phase) in the membrane. Moreover, the main phase transition becomes shifted toward a lower temperature. These results are found to be consistent with our differential scanning calorimetry measurements. Elastic intensity scans further suggest that aspirin inhibits the membrane from going into the ordered phase and overall induces disorder in the membrane, thus indicating enhancement in the fluidity of the membrane. Quasielastic neutron scattering (QENS) data show that aspirin affects both lateral lipid motion within the leaflet and the localized internal motion of the lipid. Aspirin accelerates both lateral and internal motions, with the more pronounced effect observed for the ordered phase of the neat membrane. Intermediate scattering function as observed by NSE has been analyzed using the Zilman Granek model, which indicates that addition of aspirin alters the bending modulus of the membrane to make the membrane softer. Our study provides a quantitative description of the effect of an archetypal NSAID, aspirin, on the various physical properties of the model biological membrane, which is essential for understanding the complex drug-membrane interaction.
非甾体抗炎药（NSAIDs）是世界上使用最广泛的药物之一，因其具有镇痛、解热和抗炎作用，尽管它们具有广泛的不良反应。在很大程度上，NSAIDs 的有益作用和副作用与这些药物在细胞膜水平的相互作用有关。在这里，我们使用中子散射结合弹性强度扫描、准弹性和中子自旋回波（NSE）测量来了解常用 NSAID 阿司匹林对二肉豆蔻酰磷脂酰胆碱（DMPC）膜的动力学和相行为的影响，DMPC 是存在于人红细胞膜外层的磷脂的典型代表。弹性强度扫描表明，加入阿司匹林不仅消除了预相变（固体凝胶到波纹相），而且还拓宽了膜中的主相变（波纹到流体相）。此外，主相变向更低的温度移动。这些结果与我们的差示扫描量热法测量结果一致。弹性强度扫描进一步表明，阿司匹林抑制了膜进入有序相，并使膜整体无序，从而表明膜的流动性增强。准弹性中子散射（QENS）数据表明，阿司匹林影响单层内的脂质横向运动和脂质的局部内部分子运动。阿司匹林加速了横向和内部运动，在纯膜的有序相中观察到更明显的效果。通过 NSE 观察到的中间散射函数已使用 Zilman Granek 模型进行了分析，该模型表明，加入阿司匹林会改变膜的弯曲模量，使膜变软。我们的研究提供了一种定量描述原型 NSAID 阿司匹林对模型生物膜各种物理性质的影响的方法，这对于理解复杂的药物-膜相互作用至关重要。
