Biological membranes are under constant attack of free radicals, which may lead to lipid nitro-oxidation, producing a complex mixture of nitro-oxidized lipids that are responsible for structural and dynamic changes on the membrane. Despite the latter, nitro-oxidized lipids are also associated with several inflammatory and neurodegenerative diseases, the underlying mechanisms of which remain elusive. We perform atomistic molecular dynamics simulations using several isomers of nitro-oxidized lipids to study their effect on the structure and permeability of the membrane, as well as the interaction between the mixture of these products in the phospholipid membrane environment. Our results show that the stereo- and positional isomers have a stronger effect on the properties of the membrane composed of oxidized lipids compared to that containing nitrated lipids. Nevertheless, nitrated lipids lead to three-fold increase in water permeability compared to oxidized lipids. In addition, we show that in a membrane consisting of combined nitro-oxidized lipid products, the presence of oxidized lipids protects the membrane from transient pores. This study is important to elucidate the mechanisms and the molecular level properties involving the reactive species produced during plasma application in cancer therapy as well as in photodynamic therapy, to kill cancer cells through membrane damage induced by nitro-oxidative stress.

生物膜受到自由基的不断攻击，这可能导致脂质硝基氧化，从而产生复杂的硝基氧化脂质混合物，这些混合物负责膜上的结构和动态变化。尽管有后者，但硝基氧化脂质也与几种炎性和神经退行性疾病有关，其潜在机制尚不清楚。我们使用硝基氧化脂质的几种异构体进行原子分子动力学模拟，以研究它们对膜的结构和渗透性的影响，以及这些产物的混合物在磷脂膜环境中的相互作用。我们的结果表明，与包含硝化脂质的膜相比，立体异构体和位置异构体对由氧化脂质组成的膜的性能具有更强的影响。然而，与氧化的脂质相比，硝化的脂质导致水渗透性增加了三倍。另外，我们表明在由组合的硝基氧化脂质产物组成的膜中，氧化脂质的存在可保护膜免受瞬时孔的影响。这项研究对于阐明在癌症治疗以及光动力治疗中血浆应用过程中产生的反应性物种的机制和分子水平性质，以通过硝基氧化应激诱导的膜损伤杀死癌细胞具有重要意义。与氧化的脂质相比，硝化的脂质导致水渗透性增加三倍。另外，我们表明在由组合的硝基氧化脂质产物组成的膜中，氧化脂质的存在可保护膜免受瞬时孔的影响。这项研究对于阐明在癌症治疗以及光动力治疗中血浆应用过程中产生的反应性物种的机制和分子水平性质，以通过硝基氧化应激诱导的膜损伤杀死癌细胞具有重要意义。与氧化的脂质相比，硝化的脂质导致水渗透性增加三倍。另外，我们表明在由组合的硝基氧化脂质产物组成的膜中，氧化脂质的存在可保护膜免受瞬时孔的影响。这项研究对于阐明在癌症治疗以及光动力治疗中血浆应用过程中产生的反应性物种的机制和分子水平特性，以及通过硝基氧化应激诱导的膜损伤杀死癌细胞具有重要意义。