Ionic Current Fluctuation and Orientation of Tetrahedral DNA Nanostructures in a Solid-State Nanopore.

Understanding the dynamic behavior of a nanostructure translocating through a nanopore is important for various applications. In this paper, the characteristics in ion current traces of tetrahedral DNA nanostructures (TDN) translocating through a solid-state nanopore are examined, by combined experimental and theoretical simulations. The results of finite element analysis reveal the correlation between orientation of TDN and the conductance blockade. The experimentally measured fluctuations in the conductance blockade, expressed as voltage-dependent histogram profiles, are consistent with the simulation, revealing the nature of a random distribution in orientation and weak influence of electrostatic and viscous torques. The step changes in orientation of a TDN during translocation are further explained by the collision with the nanopore, while the gradual changes in orientation illustrate the impact of a weak torque field in the nano-fluidic channel. The results demonstrate a general method and basic understanding in the dynamic behavior of nanostructures translocating through solid-state nanopores.

Detection and Characterization of Single Cisplatin Adducts on DNA by Nanopore Sequencing.

Detection and characterization of an individual cisplatin adduct on a single DNA molecule is a demanding task. We explore the characteristic features of cisplatin adducts in the nanopore sequencing signal in aspects of dwell time, genome anchored current trace, and basecalling accuracy. The offset between the motor protein and the nanopore constriction region is revealed by dwell time analysis to be about 14 bases in the nanopore device as we examined. Characteristic distortions due to cisplatin adducts are illustrated in genome anchored current trace analysis, constituting the fingerprint for identification of cisplatin adduct. The sharp increase in odds ratio at the location of adducting sites provides additional feature in the detection of the adduct. By these combined methods, single cisplatin adducts can be detected with high fidelity on a single read of the DNA sequence. The study demonstrates an effective method in the detection and characterization of single cisplatin adducts on DNA at the single-molecule level and with single nucleotide spatial resolution.

Revealing Differential Interaction Forces during Nanopore DNA Sequencing.

The interaction between DNA and the nanopore structure plays an important role in nanopore DNA sequencing. Differential interaction forces between each base type and the nanopore structure are obtained by examining the correlation between translocation dwell time and the sequence. The viscous drag force and the intermolecular interaction are identified with single-nucleotide resolution. Active hydrogen donors and acceptors on the inner wall of the nanopore structure are revealed at various offset coordinates. The differential forces as demonstrated in this study have great potential in probing active hydrogen bond interaction in a single protein molecule with subnanometer spatial resolution.