Molecular Mechanisms of Interface Interactions between Nanomaterials and Proteins
Jing-Fei HOU,Yan-Lian YANG*(),Chen WANG*()
National Center for Nanoscience and Technology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, Beijing 100190, P. R. China
Nanomaterials have excellent properties and have been used widely in chemical engineering, electronics, mechanics, environment, energy, aerospace, and many other fields in recent years. Besides, nanomaterials have attracted increasing attention in the biomedical field. The interactions between nanomaterials and protein molecules are not only significant to the basic science of the biomedical field, but also crucial for the evaluation of biomedical applications and biosafety of nanomaterials. The interfacial interactions between proteins and nanomaterials could induce a series of changes to the structures and functions of proteins, such as the transformation of protein conformations, and the modulation of aggregation states, which would influence the functions of the protein molecules. Interfacial interactions can also influence the physicochemical features of nanomaterials, including morphology, size, hydrophilicity/hydrophobicity, and surface charge density. In this review we explained the molecular level mechanisms for the interactions between nanomaterials and proteins at the interface based on the detection technologies, and discussed the changes in physical and chemical features, structures, and functions. We envision this review could be helpful for the deeper understanding of the complicated interactions between nanomaterials and proteins, and could be beneficial for promoting the healthy, safe, and sustainable development and application of nanomaterials in the biological and medical fields.
Table 1Comparison of different interactions between proteins and nanomaterials23
Fig 1 Dynamics simulation of the interaction of the graphyne sheet with the protein dimer (A) top view of the initial simulation system; (B) side view of the initial simulation system. Two protein monomers are colored in green and blue respectively. The graphyne nanosheet was placed near the dimer interface. (C) dynamic of the insertion process of the graphyne into the dimer. (a) time-dependent contact areas of the dimer during the process; (b-f) snapshots of the insertion process of the graphyne into the dimer from the fourth simulation trajectory; (b, g-k) snapshots of the insertion process of the graphyne into the dimer from the first simulation trajectory. color online (Adapted from Ref.37, Copyright 2016, American Chemical Society).
Fig 2 Inhibition of fullerene C60 and its derivatives for the Aβ peptide fibrosis top six most-populated clusters and their percentage of occupancy for (A) Aβ + C60; (B) Aβ + 3C60; (C) Aβ + C180; (D) red ones for parallel-aligned hexagons-Phe interaction and orange ones for pentagons-Phe interaction, the distances between fullerenes and the aromatic ring of amino acids are reported; (E) AFM images of Aβ + C60 with different percentage at four incubation times. color online (Adapted from Ref.52, Copyright 2014, Royal Society of Chemistry).
Fig 3 Effects of GO binding on peptide hIAPP (A) DMD structure simulation of hIAPP; (B) CD and DMD estimates of secondary structure contents of hIAPP with or without GO; (C) The hIAPP-GO binding structure, in which the aromatic residues that form π-π stacking with GO carbon atoms are highlighted with stick representation; (D) The binding is strengthened by hydrogen bonds, which is highlighted with pink dotted lines (Adapted from Ref.61, Copyright 2016, Royal Society of Chemistry).
Fig 4 isperse and selective binding of ZnO and CuO nanoparticles in the buffer (A) TEM image of ZnO NPs dispersed in medium supplemented with (a) and without (b) fetal bovine serum; (B) scattering plot of bound elements by ZnO and CuO NPs from the DMEM or DMEM with FBS, showing different binding affinities for various components of the DMEM or DMEM with FBS by the NPs; (C) various zeta potentials of ZnO and CuO NPs dispersed in different solvents. DMEM: dulbecco′s modified eagle medium, FBS: fetal bovine serus (Adapted from Ref.74, Copyright 2012, Nature).
Fig 5 Characterization of the PEGylation on GO surface, and the effects on GO binding serum proteins (A) characterization of zeta potential of GO and nGO-PEG; (B) AFM images of GO and nGO-PEG; (C) photos of GO and nGO-PEG at the same concentration; (D) Biotin-streptavidin pull-down assay. The nGO-PEG was biotinylated at PEG terminal amines, and pulled down after incubation for 1 h. Bound proteins were eluted and separated by 12% SDS-PAGE and analyzed by silver staining or LC-MS/MS identification. (E) silver staining of serum proteins associated with different GO nanosheet (Adapted from Ref.76, Copyright 2013, American Chemical Society).
Fig 6 Assembly process of peptide GrBP5 on HOPG surface (A) chemical properties and three distinct domains of GrBP5 sequence; (B) AFM image of six-fold symmetrical ordered nanostructure of GrBP5 on the graphite; (C) the FFT of the AFM image; (D) the assembly mechanism where peptides undergo binding and diffusion via domain-Ⅲ, forming rough AP, and then rearranging Domain-Ⅰ and Domain-Ⅱ folding into OP; (E) schematic of peptides assembly process on graphite, which including aggregation and ordering (Adapted from Ref.14, Copyright 2012, American Chemical Society).
Fig 7 Conformation changes of peptides induced by nanomaterials (A) STM image of peptide DELERRIRELEARIK assembly on HOPG surface; (B) CD spectra of peptide DELERRIRELEARIK with (b) and without (a) graphite particles. The presence of the peak at 213 nm is indicative of the β-sheet secondary structure induced by graphite particles. The peptide remains β-sheet secondary structure after centrifugation (c); (C) schematic model of the structural conformation of the peptide DELERRIRELEARIK; (D) STM image of peptide Vpr13-33 assembled with 4Bpy on HOPG; (E) CD spectra of Vpr13-33 with (b) and without (a) graphene oxide. The presence of the peaks at 205 and 213 nm indicates the β-sheet and β-turn induced by graphene oxide, and it remains stable after centrifugation (c); (F) the schematic illustration of mechanism how GO reduces the Vpr13-33-induced cytotoxicity (Adapted from Refs.83, 86, Copyright 2013, Elsevier; Copyright 2009, American chemical Society).
Fig 8 STM images of peptides assemblies on HOPG surface and the molecular simulation results (A) STM images of the peptide R4G4H8, and brightness contrast; (B) the relative heights of four regions (F4, R4, G4, and H8), normalized with H8 as standard reference; (C) snapshots at t=0-100 ns, with R4G4H4 cartoon representation; (D) top view and side view of R4G4H4 assembly on graphite surface (Adapted from Ref.94, Copyright 2013, American Chemical Society).
Fig 9 STM images of peptides assemblies on HOPG surface and the molecular simulation results (A) STM images of the peptide R4G4H8, and brightness contrast; (B) the relative heights of four regions (F4, R4, G4, and H8), normalized with H8 as standard reference; (C) snapshots at t=0-100 ns, with R4G4H4 cartoon representation; (D) top view and side view of R4G4H4 assembly on graphite surface (Adapted from Ref.94, Copyright 2013, American Chemical Society).
Fig 10 Multi-level heterogeneous ordered assemblies and the modifications of nanomaterials (A) Proteins are used as linkers (ⅰ) for nanoparticle immobilization, functional molecules (ⅱ) on substrates; and heterobifunctional linkers (ⅲ) for linking nanoinorganic units; (B) schematic illustration of assembly of nanogold particles on protein coated flat polystyrene surface; (C) ordered assemblies of heterogeneous nanomaterials by linking to specific proteins on ordered substrates (Adapted from Ref.12, Copyright 2003, Nature).
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