Khondker Adree, Dhaliwal Alexander, Alsop Richard J, Tang Jennifer, Backholm Matilda, Shi An-Chang, Rheinstädter Maikel C
Department of Physics and Astronomy, McMaster University, ABB-241, 1280 Main Street West, Hamilton, Ontario L8S 4M1, Canada.
Phys Chem Chem Phys. 2017 Mar 8;19(10):7101-7111. doi: 10.1039/c6cp08104e.
Caffeine is a small amphiphilic molecule, which is widely consumed as a stimulant to prevent fatigue, but is also used as a common drug adjuvant in modern medicine. Here, we show that caffeine interacts with unsaturated lipid membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). By combining X-ray diffraction and molecular dynamics simulations, we present evidence that caffeine partitions in lipid membranes and locates at the head group-tail group interface of the bilayers. By attracting water molecules from neighboring lipid molecules, it leads to the formation of "water pockets", i.e., a local increase of water density at this interface. Through this mechanism, caffeine leads to an overall decrease of the gauche defect density in the membranes and an increase of membrane thickness, indicating a loss of membrane fluidity. These non-specific membrane interactions may increase the efficacy of analgesic drugs through changes in the bioavailability and rate of metabolism of these drugs.
咖啡因是一种小分子两亲性分子，它作为一种兴奋剂被广泛食用以防止疲劳，但在现代医学中也用作常见的药物佐剂。在这里，我们表明咖啡因与由1-棕榈酰-2-油酰基-sn-甘油-3-磷酸胆碱（POPC）制成的不饱和脂质膜相互作用。通过结合X射线衍射和分子动力学模拟，我们提供了证据表明咖啡因在脂质膜中分配并位于双层膜的头部基团-尾部基团界面处。通过从相邻脂质分子吸引水分子，它导致形成“水袋”，即在该界面处水密度局部增加。通过这种机制，咖啡因导致膜中gauche缺陷密度总体降低以及膜厚度增加，表明膜流动性丧失。这些非特异性膜相互作用可能通过改变这些药物的生物利用度和代谢速率来提高镇痛药的疗效。
