Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids
Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids
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DOI：
10.1016/j.bpj.2016.12.002
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发表时间：
2017-01-24
影响因子：
3.4
通讯作者：
Levitan, Irena
中科院分区：
文献类型：
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作者：
Ayee, Manuela A. A.;LeMaster, Elizabeth;Levitan, Irena
通过计算和实验研究了两种生物活性氧化磷脂对模型双层性质、膜填充和内皮细胞生物力学的影响。截尾磷脂1-palmitoyl-2-(5-oxovaleroy1)-sn-glycero-3-phosphocholine(POVPC)和1-palmitoy1-2-glutaroyl-sn-glycero-3-phosphocholine(PGPC)是不饱和磷脂1-palmitoyl-2-arachidonoyl-sn-glycero-phosphocholine.的主要氧化产物结合粗粒分子动力学模拟、Laurdan多光子成像和原子力显微镜微压痕实验，确定POVPC和PGPC对多组分磷脂双层结构的影响，并评估它们对膜填充和内皮细胞硬度的影响。根据两种氧化磷脂截尾的化学特性，分子模拟预测了它们的不同的双分子层扰动效应，包括减少双分子层堆积、降低双分子层弯曲模数和增加透水率。脂质有序的破坏与Laurdan成像结果一致，表明POVPC和PGPC减少了有序膜结构域和无序膜结构域的脂质堆积。通过原子力显微镜测量细胞的弹性模数，可以观察到PGPC处理的内皮细胞具有更大的硬度，对PGPC产生更大的膜扰动效应的计算预测是一致的。我们的结果表明，氧化磷脂对膜结构的破坏在整体内皮细胞硬度的调节中发挥了作用。
The influence of two bioactive oxidized phospholipids on model bilayer properties, membrane packing, and endothelial cell biomechanics was investigated computationally and experimentally. The truncated tail phospholipids, 1-palmitoyl-2-(5-oxovaleroy1)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoy1-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC), are two major oxidation products of the unsaturated phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphocholine. A combination of coarse-grained molecular dynamics simulations, Laurdan multiphoton imaging, and atomic force microscopy microindentation experiments was used to determine the impact of POVPC and PGPC on the structure of a multicomponent phospholipid bilayer and to assess the consequences of their incorporation on membrane packing and endothelial cell stiffness. Molecular simulations predicted differential bilayer perturbation effects of the two oxidized phospholipids based on the chemical identities of their truncated tails, including decreased bilayer packing, decreased bilayer bending modulus, and increased water penetration. Disruption of lipid order was consistent with Laurdan imaging results indicating that POVPC and PGPC decrease the lipid packing of both ordered and disordered membrane domains. Computational predictions of a larger membrane perturbation effect by PGPC correspond to greater stiffness of PGPC-treated endothelial cells observed by measuring cellular elastic moduli using atomic force microscopy. Our results suggest that disruptions in membrane structure by oxidized phospholipids play a role in the regulation of overall endothelial cell stiffness.