Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
Phys Chem Chem Phys. 2019 Sep 18;21(36):20211-20218. doi: 10.1039/c9cp03767e.
In spite of their well-known side effects, the nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed medications for their antipyretic and anti-inflammatory actions. Interaction of NSAIDs with the plasma membrane plays a vital role in their therapeutic actions and defines many of their side effects. In the present study, we investigate the effects of three NSAIDs, aspirin, ibuprofen, and indomethacin, on the structure and dynamics of a model plasma membrane using a combination of small angle neutron scattering (SANS) and neutron spin echo (NSE) techniques. The SANS and NSE measurements were carried out on a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membrane, with and without NSAIDs, at two different temperatures, 11 °C and 37 °C, where the DMPC membrane is in the gel and fluid phase, respectively. SANS data analysis shows that incorporation of NSAIDs leads to bilayer thinning of the membrane in both the phases. The dynamic properties of the membrane are represented by the intermediate scattering functions for NSE data, which are successfully described by the Zilman and Granek model. NSE data analysis shows that in both gel and fluid phases, addition of NSAIDs results in a decrease in the bending rigidity and compressibility modulus of the membrane, which is more prominent when the membrane is in the gel phase. The magnitude of the effect of NSAIDs on the bending rigidity and compressibility modulus of the membrane in the gel phase follows an order of ibuprofen > aspirin > indomethacin, whereas in the fluid phase, it is in the order of aspirin > ibuprofen > indomethacin. We find that the interaction between NSAIDs and phospholipid membranes is strongly dependent on the chemical structure of the drugs and physical state of the membrane. Mechanical properties of the membrane can be quantified by the membrane's bending rigidity. Hence, the present study reveals that incorporation of NSAIDs modulates the mechanical properties of the membrane, which may affect several physiological processes, particularly those linked to the membrane curvature.
尽管非甾体抗炎药 (NSAIDs) 具有众所周知的副作用，但由于它们具有解热和抗炎作用，仍是最常被开处的药物之一。NSAIDs 与质膜的相互作用在其治疗作用中起着至关重要的作用，并定义了它们的许多副作用。在本研究中，我们使用小角中子散射 (SANS) 和中子自旋回波 (NSE) 技术相结合，研究了三种 NSAIDs（阿司匹林、布洛芬和吲哚美辛）对模型质膜结构和动力学的影响。SANS 和 NSE 测量分别在 1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱 (DMPC) 膜和含有和不含有 NSAIDs 的 DMPC 膜上进行，温度分别为 11°C 和 37°C，其中 DMPC 膜分别处于凝胶相和液晶相。SANS 数据分析表明，NSAIDs 的掺入导致膜在两相中均变薄。膜的动态特性由 NSE 数据的中间散射函数表示，该函数可以成功地用 Zilman 和 Granek 模型来描述。NSE 数据分析表明，在凝胶相和液晶相两种相中，加入 NSAIDs 都会导致膜的弯曲刚性和压缩模量降低，而在凝胶相时更为明显。NSAIDs 对凝胶相和液晶相膜的弯曲刚性和压缩模量的影响程度顺序为布洛芬＞阿司匹林＞吲哚美辛，而在液晶相时，则为阿司匹林＞布洛芬＞吲哚美辛。我们发现 NSAIDs 与磷脂膜的相互作用强烈依赖于药物的化学结构和膜的物理状态。膜的机械性能可以通过膜的弯曲刚性来定量。因此，本研究揭示了 NSAIDs 的掺入可以调节膜的机械性能，这可能会影响到几种生理过程，特别是与膜曲率相关的生理过程。
