title: Probing the influence of citrate-capped gold nanoparticles on an amyloidogenic protein.
abstract: Nanoparticles (NPs) are known to exhibit distinct physical and chemical properties compared with the same materials in bulk form. NPs have been repeatedly reported to interact with proteins, and this interaction can be exploited to affect processes undergone by proteins, such as fibrillogenesis. Fibrillation is common to many proteins, and in living organisms, it causes tissue-specific or systemic amyloid diseases. The nature of NPs and their surface chemistry is crucial in assessing their affinity for proteins and their effects on them. Here we present the first detailed structural characterization and molecular mechanics model of the interaction between a fibrillogenic protein, β2-microglobulin, and a NP, 5 nm hydrophilic citrate-capped gold nanoparticles. NMR measurements and simulations at multiple levels (enhanced sampling molecular dynamics, Brownian dynamics, and Poisson-Boltzmann electrostatics) explain the origin of the observed protein perturbations mostly localized at the amino-terminal region. Experiments show that the protein-NP interaction is weak in the physiological-like, conditions and do not induce protein fibrillation. Simulations reproduce these findings and reveal instead the role of the citrate in destabilizing the lower pH protonated form of β2-microglobulin. The results offer possible strategies for controlling the desired effect of NPs on the conformational changes of the proteins, which have significant roles in the fibrillation process.
authors.affiliation: †Center S3, CNR Institute Nanoscience, Via Campi 213/A, 41125 Modena, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Brancolini
authors.affiliation: ‡Dipartimento di Scienze Mediche e Biologiche (DSMB), University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy.|§Istituto Nazionale Biostrutture e Biosistemi, Viale medaglie d'Oro 305, 00136 Roma, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Corazza
authors.affiliation: ‡Dipartimento di Scienze Mediche e Biologiche (DSMB), University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Vuano
authors.affiliation: ‡Dipartimento di Scienze Mediche e Biologiche (DSMB), University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy.|§Istituto Nazionale Biostrutture e Biosistemi, Viale medaglie d'Oro 305, 00136 Roma, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Fogolari
authors.affiliation: ‡Dipartimento di Scienze Mediche e Biologiche (DSMB), University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Mimmi
authors.affiliation: §Istituto Nazionale Biostrutture e Biosistemi, Viale medaglie d'Oro 305, 00136 Roma, Italy.|⊥Dipartimento di Medicina Molecolare, Universita' di Pavia, Via Taramelli 3, 27100 Pavia, Italy.|∥Division of Medicine, University College of London, London NW3 2PF, U.K.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bellotti
authors.affiliation: §Istituto Nazionale Biostrutture e Biosistemi, Viale medaglie d'Oro 305, 00136 Roma, Italy.|⊥Dipartimento di Medicina Molecolare, Universita' di Pavia, Via Taramelli 3, 27100 Pavia, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Stoppini
authors.affiliation: †Center S3, CNR Institute Nanoscience, Via Campi 213/A, 41125 Modena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Corni
authors.affiliation: ‡Dipartimento di Scienze Mediche e Biologiche (DSMB), University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy.|§Istituto Nazionale Biostrutture e Biosistemi, Viale medaglie d'Oro 305, 00136 Roma, Italy.|¶Science and Math Division, New York University at Abu Dhabi, Abu Dhabi, UAE.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Esposito
mesh_terms: D000595:Amino Acid Sequence; D058227:Amyloidogenic Proteins / Q000737:chemistry* / Q000378:metabolism; D019343:Citric Acid / Q000737:chemistry*; D006046:Gold / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D053768:Metal Nanoparticles / Q000737:chemistry*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010316:Particle Size; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary; D055672:Static Electricity
chemical_list: D058227:Amyloidogenic Proteins; D019343:Citric Acid; D006046:Gold
keywords: amyloid; docking; fibrillogenesis; molecular dynamics; nanoparticles; nuclear magnetic resonance