Comparative Computational Study of Interaction of C60-Fullerene and Tris-Malonyl-C60-Fullerene Isomers with Lipid Bilayer: Relation to Their Antioxidant Effect
Comparative Computational Study of Interaction of C60-Fullerene and Tris-Malonyl-C60-Fullerene Isomers with Lipid Bilayer: Relation to Their Antioxidant Effect
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DOI：
10.1371/journal.pone.0102487
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发表时间：
2014-07-14
期刊：
影响因子：
3.7
通讯作者：
Shaitan, Konstantin V.
中科院分区：
文献类型：
--
作者：
Bozdaganyan, Marine E.;Orekhov, Philipp S.;Shaitan, Konstantin V.
由活性氧（ROS）的过量产生所诱导的氧化应激已经与许多人类疾病的病因学有关。据报道，富勒烯及其衍生物-羧基富勒烯-表现出很强的自由基清除能力。用分子动力学模拟方法研究了C-60-富勒烯及其两亲性衍生物C-3-tris-malonyl-C-60-富勒烯（C-3）和D-3-tris-malonyl-C-60-富勒烯（D3）通过模拟真核细胞膜的脂双层膜的渗透行为。计算了C-60、C-3和D-3分子沿1，2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）双层法线方向的自由能分布。我们发现，C-60分子单独或集群自发地易位到膜的疏水核心，并留在双层内的整个模拟时间。富勒烯团簇在双层内的掺入改变了双层的性质并导致其变形。在三丙二酸富勒烯的模拟中，我们发现两种异构体C-3和D-3吸附在双层的表面，但只有C-3倾向于被埋在与脂质尾部形成疏水接触的脂质头基的区域中。我们推测，这样的位置有影响的ROS清除机制，在特定的细胞室。
Oxidative stress induced by excessive production of reactive oxygen species (ROS) has been implicated in the etiology of many human diseases. It has been reported that fullerenes and some of their derivatives-carboxyfullerenes-exhibits a strong free radical scavenging capacity. The permeation of C-60-fullerene and its amphiphilic derivatives-C-3-tris-malonic-C-60-fullerene (C-3) and D-3-tris-malonyl-C-60-fullerene (D3)-through a lipid bilayer mimicking the eukaryotic cell membrane was studied using molecular dynamics (MD) simulations. The free energy profiles along the normal to the bilayer composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for C-60, C-3 and D-3 were calculated. We found that C-60 molecules alone or in clusters spontaneously translocate to the hydrophobic core of the membrane and stay inside the bilayer during the whole period of simulation time. The incorporation of cluster of fullerenes inside the bilayer changes properties of the bilayer and leads to its deformation. In simulations of the tris-malonic fullerenes we discovered that both isomers, C-3 and D-3, adsorb at the surface of the bilayer but only C-3 tends to be buried in the area of the lipid headgroups forming hydrophobic contacts with the lipid tails. We hypothesize that such position has implications for ROS scavenging mechanism in the specific cell compartments.