Alsop Richard J, Toppozini Laura, Marquardt Drew, Kučerka Norbert, Harroun Thad A, Rheinstädter Maikel C
Department of Physics and Astronomy, McMaster University, Hamilton, ON, Canada.
Department of Physics, Brock University, St. Catharines, ON, Canada.
Biochim Biophys Acta. 2015 Mar;1848(3):805-12. doi: 10.1016/j.bbamem.2014.11.023. Epub 2014 Dec 2.
Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin and cholesterol in lipid membranes. We have studied the effect of aspirin on the organization of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membranes containing cholesterol. Through Langmuir-Blodgett experiments we show that aspirin increases the area per lipid and decreases compressibility at 32.5 mol% cholesterol, leading to a significant increase of fluidity of the membranes. Differential scanning calorimetry provides evidence for the formation of meta-stable structures in the presence of aspirin. The molecular organization of lipids, cholesterol and aspirin was studied using neutron diffraction. While the formation of rafts has been reported in binary DPPC/cholesterol membranes, aspirin was found to locally disrupt membrane organization and lead to the frustration of raft formation. Our results suggest that aspirin is able to directly oppose the formation of cholesterol structures through non-specific interactions with lipid membranes.
阿司匹林和其他非甾体抗炎药对磷脂膜具有高亲和力，会改变其结构和生物物理性质。已表明阿司匹林可分配到脂质头部基团中，从而增加膜流动性。胆固醇是另一种众所周知的膜流动性调节剂，反过来会增加膜硬度。此外，据信胆固醇在脂质膜内分布不均，导致脂质筏或斑块的形成。在许多研究中，阿司匹林对高胆固醇患者的治疗效果更佳。我们感兴趣的是，这些作用是否至少部分是阿司匹林与脂质膜中胆固醇之间非特异性相互作用的结果。我们研究了阿司匹林对含胆固醇的1,2 - 二棕榈酰 - sn - 甘油 - 3 - 磷酸胆碱（DPPC）膜结构的影响。通过朗缪尔 - 布洛杰特实验，我们发现阿司匹林在胆固醇含量为32.5 mol%时会增加每个脂质的面积并降低可压缩性，从而导致膜流动性显著增加。差示扫描量热法为在阿司匹林存在下形成亚稳结构提供了证据。利用中子衍射研究了脂质、胆固醇和阿司匹林的分子结构。虽然在二元DPPC/胆固醇膜中已报道有筏的形成，但发现阿司匹林会局部破坏膜结构并导致筏形成受阻。我们的结果表明，阿司匹林能够通过与脂质膜的非特异性相互作用直接对抗胆固醇结构的形成。
