The nuclear pore complex (NPC) is the proteinaceous nanopore that solely mediates the transport of both small molecules and macromolecules between the nucleus and cytoplasm of a eukaryotic cell to regulate gene expression. In this personal account, we introduce recent progress in our nanoelectrochemical study of molecular transport through the NPC. Our work represents the importance of chemistry in understanding and controlling of NPC-mediated molecular transport to enable the efficient and safe delivery of genetic therapeutics into the nucleus, thereby fundamentally contributing to human health. Specifically, we employ nanoscale scanning electrochemical microscopy to test our hypothesis that the nanopore of the NPC is divided by transport barriers concentrically into peripheral and central routes to efficiently mediate the bimodal traffic of protein transport and RNA export, respectively, through cooperative hydrophobic and electrostatic interactions.

The nematode Caenorhabditis elegans is characterized by many features that make it highly attractive to study nuclear pore complexes (NPCs) and nucleocytoplasmic transport. NPC composition and structure are highly conserved in nematodes and being amenable to a variety of genetic manipulations, key aspects of nuclear envelope dynamics can be observed in great details during breakdown, reassembly, and interphase. In this chapter, we provide an overview of some of the most relevant modern techniques that allow researchers unfamiliar with C. elegans to embark on studies of nucleoporins in an intact organism through its development from zygote to aging adult. We focus on methods relevant to generate loss-of-function phenotypes and their analysis by advanced microscopy. Extensive references to available reagents, such as mutants, transgenic strains, and antibodies are equally useful to scientists with or without prior C. elegans or nucleoporin experience.