title: Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids.
abstract: 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.
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Manuela A A
authors.initials: MAA
authors.lastname: Ayee
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: LeMaster
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Tzu Pin
authors.initials: TP
authors.lastname: Shentu
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Dev K
authors.initials: DK
authors.lastname: Singh
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barbera
authors.affiliation: Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Soni
authors.affiliation: Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Chinnaswamy
authors.initials: C
authors.lastname: Tiruppathi
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Papasani V
authors.initials: PV
authors.lastname: Subbaiah
authors.affiliation: National Jewish Health, Denver, Colorado.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Berdyshev
authors.affiliation: National Jewish Health, Denver, Colorado.
authors.forename: Irina
authors.initials: I
authors.lastname: Bronova
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Michael
authors.initials: M
authors.lastname: Cho
authors.affiliation: Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina.
authors.forename: Belinda S
authors.initials: BS
authors.lastname: Akpa
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois. Electronic address: levitan@uic.edu.
authors.forename: Irena
authors.initials: I
authors.lastname: Levitan
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D055595:Mechanical Phenomena / Q000187:drug effects*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010742:Phospholipid Ethers / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; C400185:1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine; D008051:Lipid Bilayers; D010742:Phospholipid Ethers