Boonnoy Phansiri, Janlad Minchakarn, Bagheri Behnaz, Dias Cristiano, Karttunen Mikko, Wong-Ekkabut Jirasak
Department of Physics, Faculty of Science, Kasetsart University 50 Ngamwongwan Rd, Chatuchak Bangkok 10900 Thailand
Computational Biomodelling Laboratory for Agricultural Science and Technology (CBLAST), Faculty of Science, Kasetsart University 50 Ngamwongwan Rd, Chatuchak Bangkok 10900 Thailand.
RSC Adv. 2024 Sep 13;14(40):29113-29121. doi: 10.1039/d4ra04846f. eCollection 2024 Sep 12.
The presence of oxygen molecules (O) in biological membranes promotes lipid peroxidation of phospholipids with unsaturated acyl chains. On the other hand, cholesterol is considered to be an antioxidant molecule as it has a significant barrier effect on the permeation of O across membranes. However, a comprehensive explanation of how cholesterol affects the distribution and diffusion of O within lipid bilayers is yet to be established. In this study, we investigated the interaction of oxygen molecules with polyunsaturated lipid bilayers using molecular dynamics (MD) simulations. The degree of lipid unsaturation and the concentration of cholesterol were varied to study the permeation of O. The free energy profile of O diffusing from the water phase to the lipid bilayer was calculated using biased umbrella MD simulations. The results show that O passively translocates into the membrane without changing the physical properties of the bilayer. Interestingly, in the unsaturated lipid bilayers the presence of cholesterol led to a significantly decreased permeation of O and an increase in the lipid chain order. Our results indicate that the hydroxyl groups of cholesterol strongly interact with the O molecules effectively inhibiting interactions between the oxygens and the double bonds in unsaturated lipid tails. In addition, a linear relationship between permeation and the ratio of membrane thickness and area per lipid was found. These insights can help our understanding of how the degree of unsaturation in a lipid tail and cholesterol affect lipid peroxidation at the molecular level.
生物膜中氧分子（O）的存在会促进具有不饱和酰基链的磷脂发生脂质过氧化。另一方面，胆固醇被认为是一种抗氧化分子，因为它对氧跨膜渗透具有显著的屏障作用。然而，关于胆固醇如何影响脂质双层内氧的分布和扩散，尚未有全面的解释。在本研究中，我们使用分子动力学（MD）模拟研究了氧分子与多不饱和脂质双层的相互作用。通过改变脂质不饱和度和胆固醇浓度来研究氧的渗透。使用有偏伞形MD模拟计算了氧从水相扩散到脂质双层的自由能分布。结果表明，氧被动转运到膜中而不改变双层的物理性质。有趣的是，在不饱和脂质双层中，胆固醇的存在导致氧的渗透显著降低，脂质链有序度增加。我们的结果表明，胆固醇的羟基与氧分子强烈相互作用，有效地抑制了氧与不饱和脂质尾部双键之间的相互作用。此外，还发现了渗透率与膜厚度与每脂质面积比之间的线性关系。这些见解有助于我们理解脂质尾部的不饱和度和胆固醇如何在分子水平上影响脂质过氧化。
