Functional disruption in epidermal barrier enhances toxicity and accumulation of graphene oxide

In Caenorhabditis elegans, mutation of mlt-7 causes the deficits in epidermal barrier. Using the nematodes with epidermal-specific RNA interference (RNAi) knockdown of mlt-7 as a genetic tool, we found that epidermal-specific RNAi knockdown of mlt-7 resulted in a susceptibility to graphene oxide (GO) toxicity, and enhanced GO accumulation in the body. Epidermal-development related proteins of BLI-1 and IFB-1 acted as downstream targets of MLT-7, and mediated the function of MLT-7 in maintaining the epidermal barrier. Antimicrobial proteins of NLP-30 and CNC-2 also acted as downstream targets of MLT-7 in the regulation of GO toxicity. Epidermal-specific RNAi knockdown of nlp-30 or cnc-2 enhanced GO toxicity and accumulation in bli-1(RNAi) or ifb-1(RNAi) nematodes. Our data highlights the importance of maintaining normal epidermal barrier for nematodes against the GO toxicity.