The toxic differentiation of micro- and nanoplastics verified by gene-edited fluorescent Caenorhabditis elegans.

The increased emission and accumulation of micro- or nanoplastics (M-NPs) have posed a severely threaten to organisms in the environment. Though the toxicity of M-NPs has been observed in many species, the fundamental factors determining the biotoxicity are rarely expounded on. In this work, typical polystyrene (PS) M-NPs were set up with a multiparameter variation in size gradient, surface charge contrast and concentration variant, and evaluated by the Caenorhabditis elegans (C. elegans) model. From the endpoints of body length, brood size, survival rate and lifespan, an adverse effect was found on the growth and development of C. elegans caused by PSs. In general, the toxicity of PS was found to be concentrated- and size-dependent, with 100 nm positively charged nano-PS having the highest physio-toxicity. Monitoring by fluorescent imaging, it showed that positively charged nano-PS was mainly ingested and accumulated in the intestinal tract of C. elegans. In addition, the penetrated PS induced severe biological stress reactions with the increase of reactive oxygen species (ROS) and lipofuscin. Furthermore, the following expression of antioxidation-related enzymes was activated in vivo as indicated by the GFP-labelled C. elegans. All the results supplied visually toxic parameters of M-NPs to organisms, which sheds light on the biosecurity and ecological risks of M-NPs in the future.

EGCG inactivates a pore-forming toxin by promoting its oligomerization and decreasing its solvent-exposed hydrophobicity.

Natural proteinaceous pore-forming agents can bind and permeabilize cell membranes, leading to ion dyshomeostasis and cell death. In the search for antidotes that can protect cells from peptide toxins, we discovered that the polyphenol epigallocatechin gallate (EGCG) interacts directly with melittin from honeybee venom, resulting in the elimination of its binding to the cell membrane and toxicity by markedly lowering the extent of its solvent-exposed hydrophobicity and promoting its oligomerization into larger species. These physicochemical parameters have also been shown to play a key role in the binding to cells of misfolded protein oligomers in a host of neurodegenerative diseases, where oligomer-membrane binding and associated toxicity have been shown to correlate negatively with oligomer size and positively with solvent-exposed hydrophobicity. For melittin, which is not an amyloid-forming protein and has a very distinct mechanism of toxicity compared to misfolded oligomers, we find that the size-hydrophobicity-toxicity relationship also rationalizes the pharmacological attenuation of melittin toxicity by EGCG. These results highlight the importance of the physicochemical properties of pore forming agents in mediating their interactions with cell membranes and suggest a possible therapeutic approach based on compounds with a similar mechanism of action as EGCG.