Synthetic Macrocycle Nanopore for Potassium-Selective Transmembrane Transport

Dan Qiao, Himanshu Joshi, Huangtianzhi Zhu, Fushi Wang, Yang Xu, Jia Gao, Feihe Huang, Aleksei Aksimentiev, and Jiandong Feng
Journal of the American Chemical Society 143(39) 15975-15983 (2021)
DOI:10.1021/jacs.1c04910  BibTex

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Reproducing the structure and function of biological membrane channels, synthetic nanopores have been developed for applications in membrane filtration technologies and biomolecular sensing. Stable stand-alone synthetic nanopores have been created from a variety of materials, including peptides, nucleic acids, synthetic polymers, and solid-state membranes. In contrast to biological nanopores, however, furnishing such synthetic nanopores with an atomically defined shape, including deliberate placement of each and every chemical group, remains a major challenge. Here, we introduce a chemosynthetic macromolecule, extended pillararene macrocycle (EPM) as a chemically defined transmembrane nanopore that exhibits selective transmembrane transport. Our ionic current measurements reveal stable insertion of individual EPM nanopores into a lipid bilayer membrane and remarkable cation type-selective transport, with up to a 21-fold selectivity for potassium over sodium ions. Taken together, direct chemical synthesis offers a path to de novo design of a new class of synthetic nanopores with custom transport functionality imprinted in their atomically defined chemical structure.

Abstract

Reproducing the structure and function of biological membrane channels, synthetic nanopores have been developed for applications in membrane filtration technologies and biomolecular sensing. Stable stand-alone synthetic nanopores have been created from a variety of materials, including peptides, nucleic acids, synthetic polymers, and solid-state membranes. In contrast to biological nanopores, however, furnishing such synthetic nanopores with an atomically defined shape, including deliberate placement of each and every chemical group, remains a major challenge. Here, we introduce a chemosynthetic macromolecule, extended pillararene macrocycle (EPM) as a chemically defined transmembrane nanopore that exhibits selective transmembrane transport. Our ionic current measurements reveal stable insertion of individual EPM nanopores into a lipid bilayer membrane and remarkable cation type-selective transport, with up to a 21-fold selectivity for potassium over sodium ions. Taken together, direct chemical synthesis offers a path to de novo design of a new class of synthetic nanopores with custom transport functionality imprinted in their atomically defined chemical structure. 

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A rotating view of the EPM molecule illustrating the 3D structure of the nanopore. The non-hydrogen atoms constituting the constriction region of the nanopore are shown using the green spheres, whereas the Phe side chains are shown using purple spheres.

All-atom MD simulation of the EPM nanopore embedded in POPC lipid bilayer membrane and solvated in a box of water and ions. The left panel of the movie shows a cut-away view of 500 ns long MD simulation trajectory. The oxygen atom of the water molecule is shown using red spheres. The sodium and chlorides ions are shown using yellow and turquoise spheres. The central pillararene molecule is shown via green spheres whereas the Phe side chains are shown using purple spheres. The right panel of the movie simultaneously shows the side and top view of the EPM pore during the MD simulation.