Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids

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• 作者：Manuela A.A. Ayee¹ ; Elizabeth LeMaster¹ ; Tzu Pin Shentu¹ ; Dev K. Singh¹ ; Nicolas Barbera¹ ; Dheeraj Soni² ; Chinnaswamy Tiruppathi² ; Papasani V. Subbaiah³ ; Evgeny Berdyshev⁴ ; Irina Bronova⁴ ; Michael Cho⁵ ; Belinda S. Akpa⁶ ; Irena Levitan¹ ; ^{levitan@uic.edu}
• 刊名：Biophysical Journal
• 出版年：2017
• 出版时间：24 January 2017
• 年：2017
• 卷：112
• 期：2
• 页码：325-338
• 全文大小：2633 K
• 卷排序：112

文摘

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-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-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.