title: Proteomic and Lipidomic Analysis of Nanoparticle Corona upon Contact with Lung Surfactant Reveals Differences in Protein, but Not Lipid Composition.
abstract: Pulmonary surfactant (PS) constitutes the first line of host defense in the deep lung. Because of its high content of phospholipids and surfactant specific proteins, the interaction of inhaled nanoparticles (NPs) with the pulmonary surfactant layer is likely to form a corona that is different to the one formed in plasma. Here we present a detailed lipidomic and proteomic analysis of NP corona formation using native porcine surfactant as a model. We analyzed the adsorbed biomolecules in the corona of three NP with different surface properties (PEG-, PLGA-, and Lipid-NP) after incubation with native porcine surfactant. Using label-free shotgun analysis for protein and LC-MS for lipid analysis, we quantitatively determined the corona composition. Our results show a conserved lipid composition in the coronas of all investigated NPs regardless of their surface properties, with only hydrophilic PEG-NPs adsorbing fewer lipids in total. In contrast, the analyzed NP displayed a marked difference in the protein corona, consisting of up to 417 different proteins. Among the proteins showing significant differences between the NP coronas, there was a striking prevalence of molecules with a notoriously high lipid and surface binding, such as, e.g., SP-A, SP-D, DMBT1. Our data indicate that the selective adsorption of proteins mediates the relatively similar lipid pattern in the coronas of different NPs. On the basis of our lipidomic and proteomic analysis, we provide a detailed set of quantitative data on the composition of the surfactant corona formed upon NP inhalation, which is unique and markedly different to the plasma corona.
authors.affiliation: Department of Pharmacy, Saarland University , 66123 Saarbruecken, Germany.|HIPS - Helmholtz Institute for Pharmaceutical Research Saarland , Helmholtz Centre for Infection Research, 66123 Saarbruecken, Germany.
authors.forename: Simon Sebastian
authors.initials: SS
authors.lastname: Raesch
authors.affiliation: Institute of Immunology, Mainz University , 55131 Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Tenzer
authors.affiliation: Institute of Immunology, Mainz University , 55131 Mainz, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Storck
authors.affiliation: Scientific Consilience GmbH, Saarland University , 66123 Saarbruecken, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rurainski
authors.affiliation: Scientific Consilience GmbH, Saarland University , 66123 Saarbruecken, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Selzer
authors.affiliation: Department of Pharmacy, Saarland University , 66123 Saarbruecken, Germany.
authors.forename: Christian Arnold
authors.initials: CA
authors.lastname: Ruge
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University , 28040 Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Perez-Gil
authors.affiliation: Department of Pharmacy, Saarland University , 66123 Saarbruecken, Germany.
authors.forename: Ulrich Friedrich
authors.initials: UF
authors.lastname: Schaefer
authors.affiliation: Department of Pharmacy, Saarland University , 66123 Saarbruecken, Germany.|HIPS - Helmholtz Institute for Pharmaceutical Research Saarland , Helmholtz Centre for Infection Research, 66123 Saarbruecken, Germany.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D000066970:Protein Corona / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010743:Phospholipids; D000066970:Protein Corona; D011506:Proteins; D011663:Pulmonary Surfactants
keywords: biological barrier; bionano interface; bronchoalveolar lining fluid; inhalation; lipid−protein interaction; magnetic separation; nanoparticle surface