Copper nanoparticles demonstrate antibacterial activity but their toxicity to eukaryotic systems is less understood. Here, we carried out a comparative study to determine the biocompatibility and cytotoxicity of sub-10 nm copper nanoparticles to a variety of biological systems, including prokaryotic cells (Escherichia coli), yeast, mammalian cell lines (HEK293T, PC12), and zebrafish embryos. We determined the bearing threshold for the cell-death-inducing concentration of copper nanoparticles by probing cell growth, viability, as well as embryological features. To exclude the partial toxicity effect from the remnant reactants, we developed a purification approach using agarose gel electrophoresis. Purified CuONP solution inhibits bacterial growth and causes eukaryotic cell death at 170 and 122.5 ppm (w/w) during the 18 h of treatment, respectively. CuONP significantly reduces the pigmentation of retina pigmented epithelium of zebrafish embryos at 85 ppm. The cytotoxicity to eukaryotic cells could arise from the oxidative stress induced by CuONP. This result suggests that small copper nanoparticles exert cytotoxicity in both prokaryotic and eukaryotic systems, and therefore, caution should be used to avoid direct contact of copper nanoparticles to human tissues considering the potential use of copper nanoparticles in the clinical setting.

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During evolution, TRPV1 has lost, retained or selected certain residues at Lipid-Water-Interface (LWI) and formed specific patterns there. The ratio of "hydrophobic-hydrophilic" and "positive-negative charged" residues at the inner LWI remains conserved throughout vertebrate evolution and play important role in regulating TRPV1 trafficking, localization and functions. Arg575 is an important residue as Arg575Asp mutant has reduced Capsaicin-sensitivity, surface expression, colocalization with lipid-raft markers, cell area, and increased cell lethality. This lethality is due to the disruption of the ratio between positive-negative charges there. Such lethality can be rescued by either using TRPV1-specfic inhibitor 5'-IRTX or by restoring the positive-negative charge ratio at that position, i.e. by introducing Asp576Arg mutation in Arg575Asp backbone. We propose that Arg575Asp mutant confers TRPV1 in a "constitutive-open-like" condition. These findings have broader implication in understanding the molecular basis of thermo-gating and channel-gating and the microenvironments involved in such process that goes erratic in different diseases.

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