Porphyrin-Armored Gold Nanospheres Modulate the Secondary Structure of alpha-Synuclein and Arrest Its Fibrillation

摘要

The gold nanoparticle exhibits strong absorption and emission due to its unique physical geometry and surface plasmon resonance phenomena. The current investigation illustrates a unique preparation of porphyrin-functionalized gold nanosphere, photoexcited redox chemistry, and the impact of the nanosurface on protein secondary structure. Highly soluble tetrasodium salt of meso-tetrakis-(4-sulfonatophenyl)porphyrin (TPPS) in an aqueous solution initially forms 1:1 porphyrin-gold(I) static complex with a binding affinity, K-a similar to 2.1 X 10(3) M-1. Subsequently, the photosensitive porphyrin-gold(I) complex transforms into a cubic face-centered gold nanosphere, following a unique light-induced excited-state redox reaction. The observed X-ray photoelectron spectroscopy (XPS) peaks at binding energies of 83.99 and 87.6 eV corroborate to the zero oxidation state of the metal in the nanostructure. Additional peaks at 86.2 and 89.8 eV are due to the Au-O bond by the sulfonate groups of TPPS. Fourier transform infrared (FT-IR) bands at 1125, 1187, and 1208 cm(-1) are associated with different vibration modes of the SO3- groups present in TPPS, and they are largely affected as being attached to the nanosurface. The nanosphere also shows a low zeta potential value of -0.03 V and indicates a low negative charge density on the nanosurface. We further examined the interaction of this unique nanostructure with a highly soluble protein alpha-synuclein and found that the protein molecule attains a-helical/mixed secondary structure on the nanosurface. Nonetheless, it restricts the amyloid-like well-ordered beta-sheet-rich fibril formation and instead produces protein corona, encompassing the nanosurface. The protein molecules are adsorbed in a multilayer fashion, and the stoichiometric ratio between the number of proteins and a gold nanosphere is similar to 7025. The corona formation is largely stabilized by noncovalent interactions such as van der Waals and hydrogen-bond forces, and the associated thermodynamic parameters (Delta H degrees similar to -49.07 kJ mol(-1) and Delta S degrees similar to -137 J K-1 mol(-1)) are measured by isothermal calorimetric analysis. Molecular docking analysis further reveals that TPPS and gold nanosurfaces exhibit thermodynamically favorable interactions with specific amino acid residues of alpha-synuclein and thus influence the stability of the protein and its aggregation.