脂质氧化是细胞膜脂质的普遍降解过程，在多种病理生理情况下由氧化应激和活性氧和氮物种（RONS）诱导。研究表明，某些氧化脂质会改变膜特性，导致膜功能丧失。膜特性的改变被认为取决于初始膜脂组成，例如酰基链不饱和度的数量。然而，目前尚不清楚氧化损伤如何与膜的生物物理特性相关。因此，我们开始通过各种分析方法量化脂质氧化，并使用含有不同程度脂质不饱和度的脂质的模型膜确定关键的生物物理膜参数。作为 RONS 的来源，我们使用了目前开发用于治疗感染和癌症的冷血浆。我们的数据揭示了复杂的脂质氧化可能导致两种主要的透化机制。第一个出现在膜与 RONS 直接接触时，并且取决于截短的氧化磷脂的形成。这些脂质似乎部分从双层中释放出来，这意味着它们可能与其他膜相互作用并可能充当信号分子。该机制独立于脂质不饱和度，不依赖于脂质堆积的大变化，并且很可能是通过短寿命 RONS 介导的。第二种机制在较长的潜伏期后出现，并且可能取决于脂质氧加合物（例如脂质氢过氧化物或酮）的持续形成。该机制取决于脂质不饱和度并涉及脂质堆积的巨大变化。这项研究表明，存在于哺乳动物膜而不是细菌中的多不饱和脂质不会使膜对 RONS 的即时透化敏感，但可能会促进长期损伤。版权所有 © 2023 Biophysical Society。由爱思唯尔公司出版。保留所有权利。

Lipid oxidation is a universal degradative process of cell membrane lipids that is induced by oxidative stress and reactive oxygen and nitrogen species (RONS) in multiple pathophysiological situations. It has been shown that certain oxidized lipids alter membrane properties, leading to a loss of membrane function. Alteration of membrane properties is thought to depend on the initial membrane lipid composition, such as the number of acyl chain unsaturations. However, it is unclear how oxidative damage is related to biophysical properties of membranes. We therefore set out to quantify lipid oxidation through various analytical methods and determine key biophysical membrane parameters using model membranes containing lipids with different degrees of lipid unsaturation. As source for RONS we used cold plasma that is currently developed as treatment for infections and cancer. Our data revealed complex lipid oxidation that can lead to two main permeabilization mechanisms. The first one appears upon direct contact of membranes with RONS and depends on the formation of truncated oxidized phospholipids. These lipids seem to be partly released from the bilayer, implying that they are likely to interact with other membranes and potentially act as signaling molecules. This mechanism is independent of lipid unsaturation, does not rely on large variations in lipid packing and is most probably mediated via short-living RONS. The second mechanism overtakes after longer incubation periods and depends probably on the continued formation of lipid oxygen adducts such as lipid hydroperoxides or ketones. This mechanism depends on lipid unsaturation and involves large variations in lipid packing. This study indicates that polyunsaturated lipids, that are present in mammalian membranes rather than in bacteria, do not sensitize membranes to instant permeabilization by RONS but could promote long term damage.Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.