Nanoelectrochemical Study of Molecular Transport through the Nuclear Pore Complex

Abstract

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.

Nanoscale Quantitative Imaging of Single Nuclear Pore Complexes by Scanning Electrochemical Microscopy

“…17 Upon treatment with RNase, plugs changed in shape and decreased in volume as imaged by AFM, 18 thereby supporting the RNP-based plug although the volume decreased only by 18%. The RNP-based plug is consistent with the transport mechanism 19 where the NPC pore is concentrically divided into central and peripheral pathways to efficiently mediate RNA export and protein import, respectively. 20−23 Experimentally, we resolve the passive permeability of plugged and unplugged NPCs to a probe ion, i.e., tetrabutylammonium (TBA + ), by employing the SECM tips based on nanopipet-supported interfaces between two immiscible electrolyte solutions 24 (Figure 1A).…”

Nanoelectrochemistry at liquid/liquid interfaces for analytical, biological, and material applications

“…The goal of this section is to introduce the biological application of ion-selective ITIES tips for SECM studies of nanoscale molecular transport through NPCs as proteinous nanopores. 104 An important takeaway is that new gating mechanisms of the NPCs, i.e., ion-induced permeabilization 105 and electrostatic gating, 106 were discovered in these SECM studies. These findings were made by investigating the NPC-mediated transport of redoxinactive ions 105 including polyions 106 with microscale ITIES tips.…”

Recent Advances in the Glass Pipet: from Fundament to Applications

“…SECM probes are an effective tool for electrochemical quantification of biological samples. 20,106,107 Recently, Nashimoto et al 108 3.3.2. SECM Probe for Electrochemical Analysis of Inorganic Samples.…”

“…SECM probes are an effective tool for electrochemical quantification of biological samples. ,, Recently, Nashimoto et al simultaneously performed topographical and permeability analyses of a microfluidic device-based intestinal vascular model. The system was composed of two PDMS microchannels separated by a semipermeable PET membrane.…”