Department of Physics and Astronomy, McMaster University , Hamilton, Ontario L8S 4M1, Canada.
Langmuir. 2017 Aug 29;33(34):8516-8524. doi: 10.1021/acs.langmuir.7b01562. Epub 2017 Jun 8.
Curcumin is the main ingredient in turmeric, a common Indian spice. Curcumin shows a broad spectrum of effects, including anti-Alzheimer's and antioxidant properties. An interaction between curcumin and lipid membranes has been speculated as the root cause of this activity, and the molecule is often proposed to protect the bilayer. However, the detailed molecular mechanism of this protection is disputed. There is evidence that curcumin either (a) lies flat on the bilayer and provides a "carpet" for protection by forming a steric barrier, or (b) inserts into the membrane and stiffens tails, thereby protecting against peptide insertion. We studied the interaction between curcumin and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers at different concentrations using high-resolution X-ray diffraction and molecular dynamics (MD) computer simulations. We observed curcumin molecules forming a carpet in dehydrated bilayers, whereas in hydrated membranes the curcumin molecules were found to insert into the bilayers. From calculations of the potential of mean force (PMF), we find two minima, a metastable state in the headgroup region, at |z| ≈ 22 Å, and a global minimum in the hydrophobic membrane core, at |z| ≈ 9 Å. The population of the two states depends on membrane hydration. Experiments may thus observe curcumin in a carpet or inserted position, depending on the osmotic pressure conditions created, for instance, by salts, buffer solutions, substrates, or macromolecular solutes. In the carpet model, curcumin dehydrates lipid bilayers and decreases fluidity. When inserted, curcumin leads to a further fluidification of the membranes and an increase in tail fluctuations, contrary to cholesterol's condensing effect.
姜黄素是姜黄中的主要成分，姜黄是一种常见的印度香料。姜黄素显示出广泛的作用，包括抗老年痴呆症和抗氧化特性。有人推测姜黄素与脂质膜的相互作用是这种活性的根源，而且该分子通常被提议保护双层。然而，这种保护的详细分子机制存在争议。有证据表明，姜黄素要么（a）平放在双层上，并通过形成位阻障碍为保护提供“地毯”，要么（b）插入膜中并使尾部变硬，从而防止肽插入。我们使用高分辨率 X 射线衍射和分子动力学（MD）计算机模拟研究了姜黄素与 1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱（DMPC）双层在不同浓度下的相互作用。我们观察到姜黄素分子在脱水双层中形成地毯，而在水合膜中发现姜黄素分子插入双层。从平均力势（PMF）的计算中，我们发现了两个最小值，一个是在头部区域的亚稳态，|z|≈22Å，另一个是在疏水膜核心的全局最小值，|z|≈9Å。这两种状态的存在取决于膜的水合作用。因此，实验可能会观察到姜黄素处于地毯或插入位置，这取决于渗透压条件，例如由盐、缓冲溶液、底物或大分子溶质创建的渗透压条件。在地毯模型中，姜黄素使脂质双层脱水并降低流动性。当插入时，姜黄素会进一步使膜变流体化，并增加尾部波动，与胆固醇的浓缩效应相反。
