A Biomimetic Potassium Responsive Nanochannel: G-Quadruplex DNA Conformational Switching in a Synthetic Nanopore

Abstract

Potassium is especially crucial in modulating the activity of muscles and nerves whose cells have specialized ion channels for transporting potassium. Normal body function extremely depends on the regulation of potassium concentrations inside the ion channels within a certain range. For life science, undoubtedly, it is significant and challenging to study and imitate these processes happening in living organisms with a convenient artificial system. Here we report a novel biomimetic nanochannel system which has an ion concentration effect that provides a nonlinear response to potassium ion at the concentration ranging from 0 to 1500 microM. This new phenomenon is caused by the G-quadruplex DNA conformational change with a positive correlation with ion concentration. In this work, G-quadruplex DNA was immobilized onto a synthetic nanopore, which undergoes a potassium-responsive conformational change and then induces the change in the effective pore size. The responsive ability of this system can be regulated by the stability of G-quadruplex structure through adjusting potassium concentration. The situation of the grafting G-quadruplex DNA on a single nanopore can closely imitate the in vivo condition because the G-rich telomere overhang is attached to the chromosome. Therefore, this artificial system could promote a potential to conveniently study biomolecule conformational change in confined space by the current measurement, which is significantly different from the nanopore sequencing. Moreover, such a system may also potentially spark further experimental and theoretical efforts to simulate the process of ion transport in living organisms and can be further generalized to other more complicated functional molecules for the exploitation of novel bioinspired intelligent nanopore machines.

Nernst-Planck model of photo-triggered, pH–tunable ionic transport through nanopores functionalized with “caged” lysine chains

“…[13][14][15][16][17][18][19] Recent advances concerning the fabrication processes and the tailoring of the surface properties have permitted to control the pore geometry [20][21][22][23] and the response to external stimuli such as voltage, 24,25 temperature, 26,27 pH [28][29][30] or the presence of a given analyte in the pore solution. [31][32][33][34] These features have allowed the fabrication of nanofluidic devices [35][36][37][38] with potential applications in sensing, 34,39,40 energy harvesting 41,42 and information processing.…”

Chemistry Can Make Strict and Fuzzy Controls for Bio-Systems: DNA Nanoarchitectonics and Cell-Macromolecular Nanoarchitectonics

“…Instead of oligonucleotides, proton, 393,394 metal ions, 395 and metal complexes 396 were used as the fuel. In order to drive the systems, however, "photo-isomerization" is undoubtedly more preferable, since no raw materials are wasted and no byproducts are formed.…”

DNA-based switchable devices and materials

“…To understand the transportation mechanism and behavior of ions, biomolecules in the pore/channel and polymer and inorganic nanopores/nanochannels have been created. To confer on these nanopores/nanochannels stimuliresponsive properties to mimic their natural models, polymers [35,36], peptides [37] and DNA [38][39][40] have been modified onto the inner surface of nanopores/nanochannels. Among these studies, DNA has been demonstrated as an outstanding molecule to create an intelligent nanopore/nanochannel because of the clear transformation of secondary structure.…”

“…The nanopore/nanochannel has a pH-responsive conductivity change and the authors proposed that the mechanism was related to the charge densities of different DNA conformations. One year later, Hou et al [40] further studied the response mechanisms of DNAmodified nanopore/nanochannel with a potassium ion responding to a DNA sequence that is guanine (G) rich, and can fold into a four-stranded G-quadruplex in the presence of potassium ions. In the presence of lithium, they demonstrated that the G-rich sequences adopted a loosely packed single-stranded structure inside the channel (Figure 4).…”

“…Taken together, this results in interesting behaviors for this nanopore/nanochannel (Figure 4(b,c)): current first starts to drop with an increase in the concentration of potassium ions from 0 to 500 μM, which could be attributed to the increasing proportion of newly formed G-quadruplex; and with concentrations above 500 μM, currents return to a monotonous linear relation with potassium ion concentration. Hou et al [40] proposed that this was because all DNA strands were folded into the G-quadruplex under this condition. This result and proposed mechanism shows good agreement with a previous nanocontainer study.…”