Insights into the Impact of Gold Nanoclusters Au₁₀SG₁₀ on Human Microglia

Abstract

The purpose of the current study is to uncover the impact of small liganded gold nanoclusters with 10 gold atoms and 10 glutathione ligands (Au10SG10) on several biomarkers in human microglia. We established the links connecting the atomically precise structure of Au10SG10 with their properties and changes in several biomolecules under oxidative stress. Au10SG10 caused the loss of mitochondrial metabolic activity, increased lipid peroxidation and translocation of an alarmin molecule, high mobility group box 1 (HMGB1), from the nucleus to the cytosol. Molecular modeling provided an insight into the location of amino acid interaction sites with Au10SG10 and the nature of bonds participating in these interactions. We show that Au10SG10 can bind directly to the defined sites of reduced, oxidized, and acetylated HMGB1. Further studies with similar complementary approaches merging live-cell analyses, determination of biomarkers, and cell functions could lead to optimized gold nanoclusters best suited for diagnostic and bioimaging purposes in neuroscience.

Nanomaterials as Microglia Modulators in the Treatment of Central Nervous System Disorders

“…[241] Concerning gold nanomaterials (GNs), Hutter et al investigated the effects of nanostructures characterized by different morphologies, including spheres, rods, and urchins, on microglia. [242] GNs were coated with cetyltrimethylammonium bromide (CTAB) or PEG. Interestingly, the shape was demonstrated to be a key property in modulating interactions between GNs and microglial cells, and, consequently, cell activation.…”

Sulfated Hyperbranched and Linear Polyglycerols Modulate HMGB1 and Morphological Plasticity in Neural Cells

“…The MALDI MS/MS spectrum before the tryptic cleavage verified the correct mass and confirmed our previous findings that cysteines Cys23, Cys45, and Cys106 were in the fully reduced state of the commercial product (Abcam ab167718) used for the experiments. 44 These cysteines are playing a critical role in modulating the biological activity of HMGB1. When fully reduced, HMGB1 exerts chemotactic activity.…”

Open questions on proteins interacting with nanoclusters

“…As mentioned, the production of nanoclusters with atomic precision allows for unambiguously establishing the links connecting the structure of nanoclusters with their properties upon changes in several biomolecular environments. Advances in computational chemistry and hybrid calculations of large systems, e.g., with quantum mechanical (density functional)/molecular mechanical QM/MM) 17 treatment for systems containing one thousand atoms, should also make an impact on understanding the most probable binding sites for NCs within a protein molecule 14 and the effect of protein residues in controlling NC size and structure (in silico approaches) 8 . Such hybrid methods can address photophysical processes (luminescence in the linear and nonlinear optical regime) in protein-NC systems.…”

“…Once again, such an effect might be related to the capability of AuNCs to react with proteins through ligand exchange reactions. Also, similar to larger AuNCs, intracellular reactive oxygen species (ROS) generation by NCs was one of the important contributors to the mechanisms of toxicity 13 , 14 . However, the advantage of producing nanoclusters with atomic precision allows for unambiguously establishing the links connecting the structure of nanoclusters with their properties upon changes in several biomolecules under oxidative stress, as nicely exemplified with Au 10 SG 10 (see Fig.…”