title: Nanoparticle size is a critical physicochemical determinant of the human blood plasma corona: a comprehensive quantitative proteomic analysis.
abstract: In biological fluids, proteins associate with nanoparticles, leading to a protein "corona" defining the biological identity of the particle. However, a comprehensive knowledge of particle-guided protein fingerprints and their dependence on nanomaterial properties is incomplete. We studied the long-lived ("hard") blood plasma derived corona on monodispersed amorphous silica nanoparticles differing in size (20, 30, and 100 nm). Employing label-free liquid chromatography mass spectrometry, one- and two-dimensional gel electrophoresis, and immunoblotting the composition of the protein corona was analyzed not only qualitatively but also quantitatively. Detected proteins were bioinformatically classified according to their physicochemical and biological properties. Binding of the 125 identified proteins did not simply reflect their relative abundance in the plasma but revealed an enrichment of specific lipoproteins as well as proteins involved in coagulation and the complement pathway. In contrast, immunoglobulins and acute phase response proteins displayed a lower affinity for the particles. Protein decoration of the negatively charged particles did not correlate with protein size or charge, demonstrating that electrostatic effects alone are not the major driving force regulating the nanoparticle-protein interaction. Remarkably, even differences in particle size of only 10 nm significantly determined the nanoparticle corona, although no clear correlation with particle surface volume, protein size, or charge was evident. Particle size quantitatively influenced the particle's decoration with 37% of all identified proteins, including (patho)biologically relevant candidates. We demonstrate the complexity of the plasma corona and its still unresolved physicochemical regulation, which need to be considered in nanobioscience in the future.
authors.affiliation: Institute for Immunology, University Medical Center of the Johannes-Gutenberg University Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Tenzer
authors.forename: Dominic
authors.initials: D
authors.lastname: Docter
authors.forename: Susanne
authors.initials: S
authors.lastname: Rosfa
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wlodarski
authors.forename: Jörg
authors.initials: J
authors.lastname: Kuharev
authors.forename: Alexander
authors.initials: A
authors.lastname: Rekik
authors.forename: Shirley K
authors.initials: SK
authors.lastname: Knauer
authors.forename: Christoph
authors.initials: C
authors.lastname: Bantz
authors.forename: Thomas
authors.initials: T
authors.lastname: Nawroth
authors.forename: Carolin
authors.initials: C
authors.lastname: Bier
authors.forename: Jarinratn
authors.initials: J
authors.lastname: Sirirattanapan
authors.forename: Wolf
authors.initials: W
authors.lastname: Mann
authors.forename: Lennart
authors.initials: L
authors.lastname: Treuel
authors.forename: Reinhard
authors.initials: R
authors.lastname: Zellner
authors.forename: Michael
authors.initials: M
authors.lastname: Maskos
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Roland H
authors.initials: RH
authors.lastname: Stauber
mesh_terms: D006801:Humans; D013058:Mass Spectrometry; D053758:Nanoparticles; D010316:Particle Size; D010949:Plasma; D040901:Proteomics