Gudyka Jamie, Ceja-Vega Jasmin, Ivanchenko Katherine, Morocho Zachary, Panella Micaela, Gamez Hernandez Alondra, Clarke Colleen, Perez Escarlin, Silverberg Shakinah, Lee Sunghee
Department of Chemistry and Biochemistry, Iona University, 715 North Avenue, New Rochelle, New York 10801, United States.
ACS Pharmacol Transl Sci. 2024 Apr 10;7(5):1546-1556. doi: 10.1021/acsptsci.4c00093. eCollection 2024 May 10.
Growing evidence suggests that many bioactive molecules can nonspecifically modulate the physicochemical properties of membranes and influence the action of embedded membrane proteins. This study investigates the interactions of curcumin with protein-free model membranes consisting of 1,2-dioleoyl--glycero-3-phosphocholine (DOPC) and DOPC with cholesterol (4/1 mol ratio). The focus is on the capability of curcumin to modify membrane barrier properties such as water permeability assayed through the droplet interface bilayer (DIB) model membrane. For pure DOPC, our findings show a concentration-dependent biphasic effect: a reduction in water permeability is observed at low concentrations (up to 2 mol %), whereas at high concentrations of curcumin, water permeability increases. In the presence of cholesterol, we observed an overall reduction in water permeability. A combination of complementary experimental methods, including phase transition parameters studied by differential scanning calorimetry (DSC) and structural properties measured by attenuated total reflectance (ATR)-FTIR, provides a deeper understanding of concentration-dependent interactions of curcumin with DOPC bilayers in the absence and presence of cholesterol. Our experimental findings align with a molecular mechanism of curcumin's interaction with model membranes, wherein its effect is contingent on its concentration. At low concentrations, curcumin binds to the lipid-water interface through hydrogen bonding with the phosphate headgroup, thereby obstructing the transport of water molecules. Conversely, at high concentrations, curcumin permeates the acyl chain region, inducing packing disorders and demonstrating evidence of phase separation. Enhanced knowledge of the impact of curcumin on membranes, which, in turn, can affect protein function, is likely to be beneficial for the successful translation of curcumin into effective medicine.
越来越多的证据表明，许多生物活性分子可以非特异性地调节膜的物理化学性质，并影响嵌入膜蛋白的作用。本研究调查了姜黄素与由1,2-二油酰基-sn-甘油-3-磷酸胆碱（DOPC）以及DOPC与胆固醇（摩尔比4/1）组成的无蛋白模型膜之间的相互作用。重点在于姜黄素改变膜屏障特性的能力，例如通过液滴界面双层（DIB）模型膜测定的水渗透性。对于纯DOPC，我们的研究结果显示出浓度依赖性的双相效应：在低浓度（高达2 mol%）时观察到水渗透性降低，而在高浓度姜黄素时，水渗透性增加。在存在胆固醇的情况下，我们观察到水渗透性总体降低。包括通过差示扫描量热法（DSC）研究的相变参数和通过衰减全反射（ATR）-傅里叶变换红外光谱测量的结构特性在内的多种互补实验方法的结合，使我们能更深入地了解在不存在和存在胆固醇的情况下姜黄素与DOPC双层的浓度依赖性相互作用。我们的实验结果与姜黄素与模型膜相互作用的分子机制相符，其中其作用取决于浓度。在低浓度时，姜黄素通过与磷酸头部基团形成氢键结合到脂质-水界面，从而阻碍水分子的运输。相反，在高浓度时，姜黄素渗透到酰基链区域，诱导堆积紊乱并显示出相分离的迹象。深入了解姜黄素对膜的影响，进而可能影响蛋白质功能，可能有助于将姜黄素成功转化为有效的药物。
