Due to its hydrophobicity and other unique physicochemical properties, graphene oxide (GO) has been extensively utilized in various biological applications. However, introducing nanomaterials into the biological environment may raise serious risk in terms of nanotoxicity, leading to some unintended changes to the structure and the function of other biomolecules. This study investigates the interaction of GO with the ubiquitin-proteasome system, one of the essential machineries in the cellular metabolism, using a combination of experimental and computational approaches. The experimental results show that GO could adsorb the 20S proteasome, causing a dose-dependent suppression of the proteolytic activity of proteasome. This adverse effect eventually disturbed other important cellular activities relevant to cell cycle and survival. Meanwhile, the molecular dynamics simulations revealed that when 20S proteasome was adsorbed onto the graphene surface, the central gate in the outer ring (α-subunit) for the entry and the exit of the peptide ligand to the protease active site was effectively blocked. These findings of GO induced functional disturbance of 20S proteasome provides a novel perspective to understand the molecular mechanism of GO's cytotoxicity, which might further promote applications of GO in potential therapies for various cancers due to the abnormal elevation of the relevant proteasome activities.
We aimed to develop antimicrobial agents that satisfy biosafety considerations while exhibiting efficient antimicrobial activity. Peptide-capped silver nanoclusters (peptide@AgNCs) were designed. In addition, the antimicrobial activity and mechanism of peptide@AgNCs were studied. The
hemolysis and cytotoxicity tests on mammalian cells were used to confirm the biocompatibility of peptide@ AgNCs. KLA@AgNCs exhibited dramatic antimicrobial activity without inducing significant cytotoxicity in mammalian cells. The KLA@AgNCs destroyed the integrity of the bacterial membrane
and induced ROS accumulation, causing oxidative damage to biomolecules. The malfunction of the respiratory chain complexes I and V completely suppresses the energy production, ultimately accelerating the death of the bacteria. Our findings may advance the development of Ag-based nanomaterials
with enhanced bactericidal activity and improved biocompatibility.
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