We investigate the salt-dependent current modulation of bundled DNA nanostructures in a nanopore. To this end, we developed four simulation models for a 2x2 origami structure with increasing level of detail: from the mean-field level to an all-atom representation of the DNA structure. We observe a consistent pore conductivity as a function of salt concentration for all four models. However, a comparison of our data to recent experimental investigations on similar systems displays significant deviations. We discuss possible reasons for the discrepancies and propose extensions to our models for future investigations.
Graphene nanopore based sensor devices are exhibiting the great potential for the detection of DNA. To understand the fundamental aspects of DNA translocating through a graphene nanopore, in this work, molecular dynamics (MD) simulations and potential of mean force (PMF) calculations were carried out to investigate the layer impact of small graphene nanopore (2 nm-3 nm) to DNA translocation. It was observed that the ionic conductance was sensitive to graphene layer of open-nanopores, the probability for DNA translocation through graphene nanopore was related with the thickness of graphene nano…
We report an accurate method to determine DNA barcodes from the dwell time measurement of protein tags (barcodes) along the DNA backbone using Brownian dynamics simulation of a model DNA and use a recursive theoretical scheme which improves the measurements to almost 100 % accuracy. The heavier protein tags along the DNA backbone introduce a large speed variation in the chain that can be understood using the idea of non-equilibrium tension propagation theory. However, from an initial rough characterization of velocities into "fast" (nucleotides) and "slow" (protein tags) domains, we introduce …
Extracting the sequence information of DNA from the blocked ionic current is the crucial step of the ionic current-based nanopore sequencing approaches. The thinnest graphene nanopore, which contained only one layer of carbon atoms, potentially has ultra-high DNA sequencing sensitivity. However, the dynamical translocation information of DNA contained in the blocked ionic current has not been well understood to date. In this letter, an assessment to the sensitivity of ionic current-based graphene nanopore DNA sensing approach was carried out using molecular dynamics simulations. By filtering t…
Molecular dynamics simulations are used to study the equilibrium distribution of monovalent ions in a nanopore connecting two water reservoirs separated by a membrane, both for the empty pore and that with a single stranded DNA molecule inside. In the presence of DNA, the counterions condense on the stretched macromolecule effectively neutralizing it, and nearly complete depletion of coions from the pore is observed. The implications of our results for experiments on DNA translocation through alpha-hemolysin nanopores are discussed.
Ionic currents accompanying DNA translocation strongly depend on molarity of the electrolyte solution and the shape and surface charge of the nanopore. By means of the Poisson-Nernst-Planck equations it is shown how conductance is modulated by the presence of the DNA intruder and as a result of competing electrostatic and confinement factors. The theoretical results reproduce quantitatively the experimental ones and are summarized in a conductance diagram that allows distinguishing the region of reduced conductivity from the region of enhanced conductivity as a function of molarity and the por…
The translocation of double-stranded DNA through a solid-state nanopore may either decrease or increase the ionic current depending on the ionic concentration of the surrounding solution. Below a certain crossover ionic concentration, the current change inverts from a current blockade to current enhancement. In this paper, we show that the crossover concentration for bundled DNA nanostructures composed of multiple connected DNA double-helices is lower than that of double-stranded DNA. Our measurements suggest that counterion mobility in the vicinity of DNA is reduced depending on the three-dim…
We consider voltage-driving DNA translocation through a nanopore in the present study. By assuming the DNA is coaxial with the cylindrical nanopore, a hydrodynamic model for determining effective force on a single DNA molecule in a nanopore was presented, in which density functional theory (DFT) combined with the continuum Navier-Stokes (NS) equations is utilized to investigate electro-osmotic flow and the viscous drag force acting on the DNA inside a nanopore. Surface charge on the walls of the nanopore is also taken into account in our model. The consistence between our calculation and the p…
The translocation of a short DNA fragment through a nanopore is addressed when the perforated membrane contains an embedded electrode. Accurate numerical solutions of the coupled Poisson, Nernst-Planck, and Stokes equations for a realistic, fully three-dimensional setup as well as analytical approximations for a simplified model are worked out. By applying a suitable voltage to the membrane electrode, the DNA can be forced to preferably traverse the pore either along the pore axis or at a small but finite distance from the pore wall.
A solid-state nanopore can electrophoretically capture a DNA molecule and pull it through in a folded configuration. The resulting ionic current signal indicates where along its length the DNA was captured. A statistical study using an 8 nm wide nanopore reveals a strong bias favoring the capture of molecules near their ends. A theoretical model shows that bias to be a consequence of configurational entropy, rather than a search by the polymer for an energetically favorable configuration. We also quantified the fluctuations and length-dependence of the speed of simultaneously translocating pol…
We present a new concept for the separation of DNA molecules by contour length that combines a nanofluidic ratchet, nanopore translocation and pulsed fields. Using Langevin Dynamics simulations, we show that it is possible to design pulsed field sequences to ratchet captured semiflexible molecules in such a way that only short chains successfully translocate, effectively transforming the nanopore process into a low pass molecular filter. We also show that asymmetric pulses can significantly enhance the device efficiency. The process itself can be performed with many pores in parallel, and it s…
Longitudinal resolution and lateral sensitivity are decisive characteristics that determine the suitability of a nanopore sensor for sequencing a strand of DNA as well as other important polymers. Previous modeling of DNA induced ionic current blockades in single atom thick graphene nanopores has shown these nanopores to have sufficient longitudinal resolution to distinguish individual nucleobases along the length of a DNA molecule. Here we experimentally focus on the sensitivity to small changes in DNA diameter that can be discerned with graphene nanopores. We show that remarkably large sensi…
We propose two-terminal devices for DNA sequencing which consist of a metallic graphene nanoribbon with zigzag edges (ZGNR) and a nanopore in its interior through which the DNA molecule is translocated. Using the nonequilibrium Green functions combined with density functional theory, we demonstrate that each of the four DNA nucleotides inserted into the nanopore, whose edge carbon atoms are passivated by either hydrogen or nitrogen, will lead to a unique change in the device conductance. Unlike other recent biosensors based on transverse electronic transport through DNA nucleotides, which util…
We investigate the dynamics of DNA translocation through a nanopore using 2D Langevin dynamics simulations, focusing on the dependence of the translocation dynamics on the details of DNA sequences. The DNA molecules studied in this work are built from two types of bases $A$ and $C$, which has been shown previously to have different interactions with the pore. We study DNA with repeating blocks $A_nC_n$ for various values of $n$, and find that the translocation time depends strongly on the {\em block length} $2n$ as well as on the {\em orientation} of which base entering the pore first. Thus, w…
Solid-state nanopores are single molecule sensors that measure changes in ionic current as charged polymers such as DNA pass through. Here, we present comprehensive experiments on the length, voltage and salt dependence of the frequency of double-stranded DNA translocations through conical quartz nanopores with mean opening diameter 15 nm. We observe an entropic barrier limited, length dependent translocation frequency at 4M LiCl salt concentration and a drift-dominated, length independent translocation frequency at 1M KCl salt concentration. These observations are described by a unifying conv…
The threading of a polymer chain through a small pore is a classic problem in polymer dynamics and underlies nanopore sensing technology. However important experimental aspects of the polymer motion in a solid-state nanopore, such as an accurate measurement of the velocity variation during translocation, have remained elusive. In this work we analysed the translocation through conical quartz nanopores of a 7 kbp DNA double-strand labelled with six markers equally spaced along its contour. These markers, constructed from DNA hairpins, give direct experimental access to the translocation dynamic…
Recent experiments of translocation of double stranded DNA through nanopores [M. Wanunu \textit{et al.} Nature Nanotech. {\bf 5}, 160 (2010)] reveal that the DNA capture rate can be significantly influenced by a salt gradient across the pore. We show that osmotic flow combined with electrophoretic effects can quantitatively explain the experimental data on the salt-gradient dependence of the capture rate.
Ultrathin membranes have drawn much attention due to their unprecedented spatial resolution for DNA nanopore sequencing. However, the high translocation velocity (3000-50000 nt/ms) of DNA molecules moving across such membranes limits their usability. To this end, we have introduced a viscosity gradient system based on room-temperature ionic liquids (RTILs) to control the dynamics of DNA translocation through a nanometer-size pore fabricated in an atomically thin MoS2 membrane. This allows us for the first time to statistically identify all four types of nucleotides with solid state nanopores. …
Recent work has shown that the resistive force arising from viscous effects within the pore region could explain [Ghosal, S. Phys. Rev. E. vol. 71, 051904 (2006) and Phys. Rev. Lett. vol. 98, 238104 (2007)] observed translocation times in certain experiments involving voltage driven translocations of DNA through nanopores. The electrokinetic flow inside the pore and the accompanying viscous effects also play a crucial role in the interpretation of experiments where the DNA is immobilized inside a nanopore[U. Keyser, et al., Nature Physics vol. 2, 473 (2006)]. In this paper the viscous force is…
Translocation of a single stranded DNA through genetically engineered $α$-hemolysin channels with positively charged walls is studied. It is predicted that transport properties of such channels are dramatically different from neutral wild type $α$-hemolysin channel. We assume that the wall charges compensate the fraction $x$ of the bare charge $q_{b}$ of the DNA piece residing in the channel. Our prediction are as follows (i) At small concentration of salt the blocked ion current decreases with $x$. (ii) The effective charge $q$ of DNA piece, which is very small at $x = 0$ (neutral channel) gr…
The potential of a double nanopore system to determine DNA barcodes has been demonstrated experimentally. By carrying out Brownian dynamics simulation on a coarse-grained model DNA with protein tag (barcodes) at known locations along the chain backbone, we demonstrate that due to large variation of velocities of the chain segments between the tags, it is inevitable to under/overestimate the genetic lengths from the experimental current blockade and time of flight data. We demonstrate that it is the tension propagation along the chain's backbone that governs the motion of the entire chain and i…
We investigate the ionic current modulation in DNA nanopore translocation setups by numerically solving the electrokinetic mean-field equations for an idealized model. Specifically, we study the dependence of the ionic current on the relative length of the translocating molecule. Our simulations show a significantly smaller ionic current for DNA molecules that are shorter than the pore at low salt concentrations. These effects can be ascribed to the polarization of the ion cloud along the DNA that leads to an opposing electric dipole field. Our results for DNA shine light on the observed discr…
Double-stranded DNA translocates through sufficiently large nanopores either in a linear, single-file fashion or in a folded hairpin conformation when captured somewhere along its length. We show that the folding state of DNA can be controlled by changing the electrolyte concentration, pH and PEG content of the measurement buffer. At 1 M LiCl or 0.35 M KCl in neutral pH, single-file translocations make up more than 90% of the total. We attribute the effect to the onset of electroosmotic flow from the pore at low ionic strength. Our hypothesis on the critical role of flows is supported by the p…
We studied the unzipping kinetics of single molecules of double-stranded DNA by pulling one of their two strands through a narrow protein pore. PCR analysis yielded the first direct proof of DNA unzipping in such a system. The time to unzip each molecule was inferred from the ionic current signature of DNA traversal. The distribution of times to unzip under various experimental conditions fit a simple kinetic model. Using this model, we estimated the enthalpy barriers to unzipping and the effective charge of a nucleotide in the pore, which was considerably smaller than previously assumed.
Flow-driven rotary motors drive functional processes in human society such as windmills and water wheels. Although examples of such rotary motors also feature prominently in cell biology, their synthetic construction at the nanoscale has thus far remained elusive. Here, we demonstrate flow-driven rotary motion of a self-organized DNA nanostructure that is docked onto a nanopore in a thin solid-state membrane. An elastic DNA bundle self assembles into a chiral conformation upon phoretic docking onto the solid-state nanopore, and subsequently displays a sustained unidirectional rotary motion of …
Motivated by DNA electrophoresis near a nanopore, we consider the flow field around an "elongated jet", a long thin source which injects momentum into a liquid. This solution qualitatively describes the electro-osmotic flow around a long rigid polymer, where due to electrohydrodynamic coupling, the solvent receives momentum from the electric field. Based on the qualitative behavior of the elongated jet solution, we develop a coarse-grained scheme which reproduces the known theoretical results regarding the electrophoretic behavior of a long rigid polymer and a polymer coil in a uniform field, …
Based on our formulation of the DNA electrophoresis near a pore [P. Rowghanian and A. Y. Grosberg, Phys. Rev. E 87, 042723 (2013)], we address the electrophoretic DNA capture into a nanopore as a steady-state process of particle absorption to a sink placed on top of an energy barrier. Reproducing the previously observed diffusion-limited and barrier-limited regimes as two different limits of the particle absorption process and matching the data, our model suggests a slower growth of the capture rate with the DNA length for very large DNA molecules than the previous model, motivating more exper…
Using first-principles quantum transport simulations, based on the nonequilibrium Green function formalism combined with density functional theory (NEGF+DFT), we examine changes in the total and local electronic currents within the plane of graphene nanoribbon with zigzag edges (ZGNR) hosting a nanopore which are induced by inserting a DNA nucleobase into the pore. We find a sizable change of the zero-bias conductance of two-terminal ZGNR + nanopore device after the nucleobase is placed into the most probable position (according to molecular dynamics trajectories) inside the nanopore of a smal…
We investigate the translocation of a single stranded DNA (ssDNA) through a pore, which fluctuates between two conformations, by using coupled master equations (ME). The probability density function (PDF) of the first passage times (FPT) of the translocation process is calculated, displaying a triple, double or mono-peaked behavior, depending on the system parameters. An analytical expression for the mean first passage time (MFPT) of the translocation process is derived, and provides an extensive characterization of the translocation process.
In this short note, a correction is made to the recently proposed solution [1] to a 1D biased diffusion model for linear DNA translocation and a new analysis will be given to the data in [1]. It was pointed out [2] by us recently that this 1D linear translocation model is equivalent to the one that was considered by Schrodinger [3] for the Enrenhaft-Millikan measurements [4,5] on electron charge. Here we apply Schrodinger's first-passage-time distribution formula to the data set in [1]. It is found that Schrodinger's formula can be used to describe the time distribution of DNA translocation in…
Using theory and simulations, we carried out a first systematic characterization of DNA unzipping via nanopore translocation. Starting from partially unzipped states, we found three dynamical regimes depending on the applied force, f: (i) heterogeneous DNA retraction and rezipping (f < 17pN), (ii) normal (17pN < f < 60pN) and (iii) anomalous (f > 60pN) drift-diffusive behavior. We show that the normal drift-diffusion regime can be effectively modelled as a one-dimensional stochastic process in a tilted periodic potential. We use the theory of stochastic processes to recover the potential from …
The capture and translocation of biomolecules through nanometer-scale pores are processes with a potential large number of applications, and hence they have been intensively studied in the recent years. The aim of this paper is to review existing models of the capture process by a nanopore, together with some recent experimental data of short single- and double-stranded DNA captured by Cytolysin A (ClyA) nanopore. ClyA is a transmembrane protein of bacterial origin which has been recently engineered through site-specific mutations, to allow the translocation of double- and single-stranded DNA.…
We investigate the dynamics of DNA translocation through a nanopore driven by an external force using Langevin dynamics simulations in two dimensions (2D) to study how the translocation dynamics depend on the details of the DNA sequences. We consider a coarse-grained model of DNA built from two bases $A$ and $C$, having different base-pore interactions, {\textit e.g.}, a strong (weak) attractive force between the pore and the base $A$ ($C$) inside the pore. From a series of studies on hetero-DNAs with repeat units $A_mC_n$, we find that the translocation time decreases exponentially as a funct…
We report translocation experiments on double-strand DNA through a silicon oxide nanopore. Samples containing DNA fragments with seven different lengths between 2000 to 96000 basepairs have been electrophoretically driven through a 10 nm pore. We find a power-law scaling of the translocation time versus length, with an exponent of 1.26 $\pm$ 0.07. This behavior is qualitatively different from the linear behavior observed in similar experiments performed with protein pores. We address the observed nonlinear scaling in a theoretical model that describes experiments where hydrodynamic drag on the…
The passage of DNA through a nanopore can be effectively decomposed into two distinct phases, docking and actual translocation. In experiments each phase is characterized by a distinct current signature which allows the discrimination of the two events. However, at low voltages a clear distinction of the two phases is lost. By using numerical simulations we clarify how the current signature associated to the docking events depends on the applied voltage. The simulations show that at small voltage the DNA globule enhances the pore conductance due to an enrichment of charge carriers. At high vol…
We predict streaming current inversion with multivalent counterions in hydrodynamically driven polymer translocation events from a correlation-corrected charge transport theory including charge fluctuations around mean-field electrostatics. In the presence of multivalent counterions, electrostatic many-body effects result in the reversal of the DNA charge. The attraction of anions to the charge-inverted DNA molecule reverses the sign of the ionic current through the pore. Our theory allows for a comprehensive understanding of the complex features of the resulting streaming currents. The underl…
We consider the influence of electrostatic forces on driven translocation dynamics of a flexible polyelectrolyte being pulled through a nanopore by an external force on the head monomer. To this end, we augment the iso-flux tension propagation (IFTP) theory with electrostatics for a negatively charged biopolymer pulled through a nanopore embedded in a similarly charged anionic membrane. We show that for the realistic case such as a single-stranded DNA, the translocation dynamics at low salt where screening is weak and at finite negative membrane charge is unexpectedly accelerated despite the l…
DNA capture with high fidelity is an essential part of nanopore translocation. We report several important aspects of the capture process and subsequent translocation of a model DNA polymer through a solid-state nanopore in presence of an extended electric field using the Brownian dynamics simulation that enables us to record statistics of the conformations at every stage of the translocation process. By releasing the equilibrated DNAs from different equipotentials, we observe that the capture time distribution depends on the initial starting point and follows a Poisson process. The field grad…
We investigate the translocation of a single stranded DNA through a pore which fluctuates between two conformations, using coupled master equations. The probability density function of the first passage times (FPT) of the translocation process is calculated, displaying a triple, double or mono peaked behavior, depending on the interconversion rates between the conformations, the applied electric field, and the initial conditions. The cumulative probability function of the FPT, in a field-free environment, is shown to have two regimes, characterized by fast and slow timescales. An analytical ex…
The determination of a patient's DNA sequence can, in principle, reveal an increased risk to fall ill with particular diseases [1,2] and help to design "personalized medicine" [3]. Moreover, statistical studies and comparison of genomes [4] of a large number of individuals are crucial for the analysis of mutations [5] and hereditary diseases, paving the way to preventive medicine [6]. DNA sequencing is, however, currently still a vastly time-consuming and very expensive task [4], consisting of pre-processing steps, the actual sequencing using the Sanger method, and post-processing in the form …
Recent years have seen a surge of interest in nanopores because such structures show a strong potential for characterizing nanoparticles, proteins, DNA, and even single molecules. These systems have been extensively studied in experiment as well as by all-atom and coarse-grained simulations, with a strong focus on DNA translocation. However, the equally interesting problem of particle characterization using nanopores has received far less attention. Here, we theoretically investigate the translocation of a nanoparticle through a conical nanocapillary. We use a model based on numerically solvin…
The translocation of structured RNA or DNA molecules through narrow pores necessitates the opening of all base pairs. Here, we study the interplay between the dynamics of translocation and base-pairing theoretically, using kinetic Monte Carlo simulations and analytical methods. We find that the transient formation of basepairs that do not occur in the ground state can significantly speed up translocation.
Engineering the synthetic nanopores through lipid bilayer membrane to access the interior of a cell is a long persisting challenge in biotechnology. Here, we demonstrate the stability and dynamics of a tile-based 6-helix DNA nanotube (DNT) embedded in POPC lipid bilayer using the analysis of 0.2 microsecond long equilibrium MD simulation trajectories. We observe that the head groups of the lipid molecules close to the lumen cooperatively tilt towards the hydrophilic sugar-phosphate backbone of DNA and form a toroidal structure around the patch of DNT protruding in the membrane. Further, we exp…
DNA translocation through nanopores is one of the most promising strategies for the next-generation sequencing technologies. Most part of experimental and numerical works has focused on polymer translocation biased by electrophoresis, where a pulling force acts on the polymer within the nanopore. An alternative strategy however is emerging, which uses optical or magnetic tweezers. In this case, the pulling force is exerted directly at one end of the polymer, which strongly modifies the translocation process. In this paper, we report numerical simulations of both linear and structured (mimickin…
We investigate theoretically the translocation of structured RNA/DNA molecules through narrow pores which allow single but not double strands to pass. The unzipping of basepaired regions within the molecules presents significant kinetic barriers for the translocation process. We show that this circumstance may be exploited to determine the full basepairing pattern of polynucleotides, including RNA pseudoknots. The crucial requirement is that the translocation dynamics (i.e., the length of the translocated molecular segment) needs to be recorded as a function of time with a spatial resolution o…
We study theoretically the feasibility of using transverse electronic transport within a nanopore for rapid DNA sequencing. Specifically, we examine the effects of the environment and detection probes on the distinguishability of the DNA bases. We find that the intrinsic measurement bandwidth of the electrodes helps the detection of single bases by averaging over the current distributions of each base. We also find that although the overall magnitude of the current may change dramatically with different detection conditions, the intrinsic distinguishability of the bases is not significantly af…
Previous theoretical studies have shown that measuring the transverse current across DNA strands while they translocate through a nanopore or channel may provide a statistically distinguishable signature of the DNA bases, and may thus allow for rapid DNA sequencing. However, fluctuations of the environment, such as ionic and DNA motion, introduce important scattering processes that may affect the viability of this approach to sequencing. To understand this issue, we have analyzed a simple model that captures the role of this complex environment in electronic dephasing and its ability to remove…
We investigate the impact of dielectric boundary forces on the translocation process of charged rigid DNA segments through solid neutral nanopores. We assess the electrostatic contribution to the translocation free energy barrier of a model DNA segment by evaluating the potential of mean force in absence and presence of polarization effects by means of coarse-grained molecular dynamics simulations. The effect of induced polarization charges has been taken into account by employing ICC*, a recently developed algorithm that can efficiently compute induced polarization charges induced on suitably…
Polymer translocation experiments typically involve anionic polyelectrolytes such as DNA molecules driven through negatively charged nanopores. Quantitative modelling of polymer capture to the nanopore followed by translocation therefore necessitates the consideration of the electrostatic barrier resulting from like-charge polymer-pore interactions. To this end, in this work we couple mean-field level electrohydrodynamic equations with the Smoluchowski formalism to characterize the interplay between the electrostatic barrier, the electrophoretic drift, and the electro-osmotic liquid flow. In p…
