Translocation Time Research Articles

A Monte Carlo study on a 3-dimensional comb polymer translocation through a nanopore driven by an electric field

Abstract A lattice Monte Carlo simulation study of the translocation of comb polymers through a nanopore subjected to an electric field is presented. The translocation dynamics was extensively studied in terms of the applied electric field strength, the pore size, and the comb polymer topology. The variations of the most probable translocation time $\tau_p$ and the mean translocation time \mt\ as a function of the applied electric field strength show distinct features, the latter exhibiting a nonmonotonic dependence on the electric field. We were able to show the existence of a critical field strength $\delta \epsilon_c$ defined by the narrowest distribution of the translocation time, which is closely related to the size of the nanopore. In addition, we have found that the critical field strength also defines a transition point between two regimes of translocation: a smooth translocation for a field strength below $\delta \epsilon_c$ and a chaotic translocation for a field strength above $\delta \epsilon_c$. Moreover, for the smallest pore size ($r_p = 1$), monomers can only cross the nanopore in a single file, while for larger pores different modes of polymer translocation are identified. Finally, the dependence of the mean translocation time on the backbone length is governed by a power law relationship $\left < \tau \right > \sim {N_B}^{\alpha}$, where the scaling exponent $\alpha$ is found to be in the range of 1.3--1.7 for the set of side chain lengths and nanopore sizes investigated. As for the side chain length $N_S$, the mean translocation time is found to follow a linear dependence $\left < \tau \right > \sim {N_S}$.

Translocation of Gaussian polymers across a nanometric cylindrical channel

We present an analytical model to study translocation of Gaussian polymers across a cylindrical channel of nanometric size with a chemical potential inside the channel. Results show that polymer conformational entropy generates an entropic M-like free energy barrier for translocation. The presence of a small negative chemical potential reduces the entropic free energy barrier rendering the translocation time to follow a power law τ = AN ν as function of polymer size N. Power law exponents ν found here in varying the channel radius R, run from 1.525 to 1.999 for unforced translocation, and from 1.594 to 2.006 for translocation with small chemical potentials when R = 1 nm. Presence of large negative chemical potentials generate a free energy well rendering the translocation time to follow an exponential growth τ = Ae α N . We show existence of a negative chemical potential μ c that minimizes the translocation time due to an interplay of conformational entropy and channel-polymer interactions. The translocation time as function of channel length L grows exponentially as τ = Ae cL , it runs from milliseconds up to decades in the range of lengths found in biological channels. Interestingly, small negative chemical potentials approaching μ c overcome the effect of large channel lengths reducing the translocation time below seconds. Translocation speeds <v(N) > show a maximum of micrometers per second then it decays with polymer size and channel length, the characteristic decay <v(N) > ∼ N −1 has been observed in previous experiments of voltage-driven DNA translocation.

Transport of a comb-like polymer across a nanochannel subject to a pulling force.

We investigate the dynamics of comb-like polymer translocation through a nanochannel using three-dimensional Langevin dynamics simulations based on a coarse-grained chain model. A comprehensive set of simulations are performed to examine the effects of system parameters such as the grafting densityρof the side chains, the polymer chain length, the nanochannel dimensions, and the magnitude of the pulling force on the translocation dynamics. For a given polymer chain length, keeping the backbone length is constant while varyingρ, we have found that the dependence of the mean translocation time⟨τ⟩onρis non-monotonic, with a maximum translocation time for a specificρat which the translocation is the slowest. The simulation results also show that⟨τ⟩is not significantly affected by the channel width above a certain radius, while the comb-like polymer translocation is hindered by a narrower channel due to increased interactions between the chain monomers and the channel. In addition,⟨τ⟩increases linearly with the nanochannel length. A linear scaling relationship between the mean translocation time⟨τ⟩and the chain lengthNof polymer is obtained,⟨τ⟩∼N. Similarly, the dependence of⟨τ⟩on the backbone chain sizeNbbhas a quasi-linear dependence,⟨τ⟩∼Nbb. On the other hand, the translocation velocityvfollows a power-law relationship with the polymer chain lengthNasv∼N-1. The mean translocation time also shows an inverse linear relationship with the magnitude of the pulling forceF,⟨τ⟩∼F-1. The power-law relationships discovered in this study contribute to the fundamental understanding of the comb polymer translocation dynamics and to establishing a framework for further investigations in this field.

Langevin Dynamics Study on the Driven Translocation of Polymer Chains with a Hairpin Structure.

The hairpin structure is a common and fundamental secondary structure in macromolecules. In this work, the process of the translocation of a model polymer chain with a hairpin structure is studied using Langevin dynamics simulations. The simulation results show that the dynamics of hairpin polymer translocation through a nanopore are influenced by the hairpin structure. Hairpin polymers can be classified into three categories, namely, linear-like, unsteady hairpin, and steady hairpin, according to the interaction with the stem structure. The translocation behavior of linear-like polymers is similar to that of a linear polymer chain. The time taken for the translocation of unsteady hairpin polymers is longer than that for a linear chain because it takes a long time to unfold the hairpin structure, and this time increases with stem interaction and decreases with the driving force. The translocation of steady hairpin polymers is distinct, especially under a weak driving force; the difficulty of unfolding the hairpin structure leads to a low translocation probability and a short translocation time. The translocation behavior of hairpin polymers can be explained by the theory of the free-energy landscape.

A Semiflexible Polymer Translocation Through a Cylindrical Channel

In this study, translocation of a semi flexible polymer through a cylindrical channel have been investigated. A two-dimensional Monte Carlo simulation was employed, by utilizing the bond fluctuation method (BFM) to investigate the translocation processes of a chain length N. To surmount the entropic barrier, the middle monomers of the polymer have been positioned at the center of the pore, which is situated between the CIS and TRANS regions. Consequently, the static properties of a semi-flexible polymer by calculating the mean square end-to-end distance ‹R2› and the mean square radius of gyration ‹R&amp;lt;sup&amp;gt;g&amp;lt;/sup&amp;gt;2› as functions of the chain length (N) have been examined. The mean square end-to-end distance and the mean square radius of gyration are proportional to the number of monomers N as ‹R2› ~ N1.496 and ‹R2g› ~ N1.505 correspondingly for a short cylindrical channel length L = 2, which aligns with the theoretically predicted. These finding indicates that the relationships between ‹R2› and ‹R&amp;lt;sup&amp;gt;g&amp;lt;/sup&amp;gt;2› and the polymer chain size N are strongly influenced by the channel length L. The dynamic properties by analyzing the translocation time of the polymers also studied. Additionally, the relationship between the escape time τ and the polymer chain length N depends on the pore width W, which is equivalent to the diameter of the cylindrical channel. These research demonstrates that the escape time τ decreases as the width increases and escape time τ increases as the chain stiffness increases.

Controlling DNA Fragments Translocation across Nanopores with the Synergic Use of Site-Directed Mutagenesis, pH-Dependent Charge Tuning, and Electroosmotic Flow.

Biological and solid-state nanopores are at the core of transformative techniques and nanodevices, democratizing the examination of matter and biochemical reactions at the single-molecule level, with low cost, portability, and simplicity in operation. One of the crucial hurdles in such endeavors is the fast analyte translocation, which limits characterization, and a rich number of strategies have been explored over the years to overcome this. Here, by site-directed mutagenesis on the α-hemolysin protein nanopore (α-HL), sought to replace selected amino acids with glycine, electrostatic binding sites were induced on the nanopore's vestibule and constriction region and achieved in the most favorable case a 20-fold increase in the translocation time of short single-stranded DNA (ssDNA) at neutral pH, with respect to the wild-type (WT) nanopore. We demonstrated an efficient tool of controlling the ssDNA translocation time, via the interplay between the nanopore-ssDNA surface electrostatic interactions and electroosmotic flow, all mediated by the pH-dependent ionization of amino acids lining the nanopore's translocation pathway. Our data also reveal the nonmonotonic, pH-induced alteration of ssDNA average translocation time. Unlike mildly acidic conditions (pH ∼ 4.7), at a pH ∼ 2.8 maintained symmetrically or asymmetrically across the WT α-HL, we evidenced the manifestation of a dominant electroosmotic flow, determining the speeding up of the ssDNA translocation across the nanopore by counteracting the ssDNA-nanopore attractive electrostatic interactions. We envision potential applications of the presented approach by enabling easy-to-use, real-time detection of short ssDNA sequences, without the need for complex biochemical modifications to the nanopore to mitigate the fast translocation of such sequences.

Label-free detection of glutathione and glutathione disulfide in biological fluid by using an alpha-hederin nanopore

Glutathione (GSH) is indispensable for maintaining redox homeostasis in biological fluids and serves as a key component in cellular defense mechanisms. Accurate assessment of GSH relative to its oxidized counterpart, glutathione disulfide (GSSG), is critical for the early diagnosis and understanding of conditions related to oxidative stress. Despite existing methods for their quantification, the label-free and simultaneous measurement of GSH and GSSG in biological fluid presents significant challenges. Herein, we report the use of an alpha-hederin (Ah) nanopore for the direct measurement of the GSH:GSSG ratio in simulated biological fluid, containing fetal bovine serum (FBS). This system hinges on detecting characteristic relative ion blockades (ΔI/Io) as GSH and GSSG molecules pass through the Ah nanopore under an applied electric field. The distinct current blockage signals derived from the translocation of GSH and GSSG enabled us to determine the molar ratio of GSH and its oxidized form. Notably, the interactions between the hydroxyl groups of the sugar moiety lining the nanopore's inner surface and the sulfhydryl group of GSH significantly influence the translocation dynamics, resulting in a longer translocation time for GSH compared to GSSG. The Ah nanopore technology proposed in this study offers a promising approach for real-time, single molecule-level monitoring of glutathione redox status in biological fluids, eliminating the need for labeling or extensive sample preparation.

Water transport in double-walled carbon nanotubes

Water confined in nanoscale environments exhibits rich phase behaviors. Recently, double-walled carbon nanotubes (DWCNTs) have been found to be able to generate ice nanotubes with large sizes, but their dynamics are still not explored. In this work, upon using molecular dynamics simulations we systematically investigate the water transport in DWCNTs, focusing on the effect of CNT length and temperature. At low temperatures, with the increase in CNT length, the water flow decreases linearly first and then has a sudden reduction to zero because of the liquid-ice phase transition; while at high temperatures the water flow decreases linearly without freezing. Obviously, the critical CNT length for the formation of ice increases at higher temperatures, because longer CNTs facilitate the ordered water structures. Furthermore, for a short CNT the water flow exhibits a perfect linear increase with the temperature; while for long CNTs, the water flow is zero at low temperatures because of the ice phase, and then increases suddenly. Apparently, the critical melting temperature shifts to higher values for longer CNTs. The translocation time has an overall opposite behavior compared to the water flow, and the water occupancy and dipole orientation are also sensitive to the CNT length and temperature. Our results reveal the relationship between water structures and dynamics within DWCNTs, and should have great implications for the design of novel nanofluidic devices.

Translocation of two-dimensional active polymers through nanopores using Langevin dynamics simulations.

The translocation of polymers through nanopores is a complex process influenced by various factors. In this study, the translocation behavior of a two-dimensional active polymer chain, comprised of a head active Brownian particle (ABP) and a tail passive polymer chain, through a nanopore is studied using Langevin dynamics simulations. Results show that the effect of the self-propulsion force of the ABP on the translocation differs significantly from the driving force inside the pore for traditional polymer translocations. Specifically, the translocation time τ initially increases with increasing the magnitude fs of the self-propulsion force and then decreases with a further increase in fs. A small fs lowers the potential barrier for the translocation and thus promotes slow translocations, whereas a large fs directly pulls the polymer chain through the nanopore following the scaling relation τ ∝ fs-1. Moreover, two asymptotic scaling relations between τ and polymer length N, τ ∝ Nα, are found, with the exponent α of about 2.5 for small fs or long N and the exponent α of about 1.4 for short active polymers with large fs. We discover that the slow rotation of the ABP accelerates the translocation process.

Translocation of polymers through a wide-open conical pore

The transport of biomolecules across a cell membrane is an important phenomenon that plays a pivotal role in the functioning of biological cells. In this paper, we investigate such processes by modeling the translocation of polymers through a conical channel, directed from the wider opening to the narrow end of the conical channel. We use the molecular dynamics approach to study the problem. The effect of the different conical pore geometry and polymer lengths on translocation dynamics is determined from the behavior of the total translocation time, τ, and the waiting time distributions, w(s). The escape of polymer segments from the narrow end of the conical channel is tracked by studying the escape velocity profile (〈v i 〉). To demonstrate the asymmetric pore effects on the translocation dynamics, we compare the translocation process from both the terminals: the wider-opening and the narrow-end of the conical channel. We find striking differences in the translocation dynamics for both processes, which are in agreement with the experimental study. We have accounted for the effect of various rigidity, and increasing length of a polymer chain, on both types of processes. This computational study can be used to underline the translocation process from different conical pores.

Na+-Mg2+ ion effects on conformation and translocation dynamics of single-stranded RNA: Cooperation and competition

The nanopore-based translocation of a single-stranded RNA (ssRNA) in mixed salt solution has garnered increasing interest for its biological and technological significance. However, it is challenging to comprehensively understand the effects of the mixed ion species on the translocation dynamics due to their cooperation and competition, which can be directly reflected by the ion screening and neutralizing effects, respectively. In this study, Langevin dynamics simulation is employed to investigate the properties of ssRNA conformation and translocation in mixed Na+-Mg2+ ion environments. Simulation results reveal that the ion screening effect dominates the change in the ssRNA conformational size, the ion neutralizing effect controls the capture rate of the ssRNA by the nanopore, and both of them take charge of the different changes in translocation time of the ssRNA under various mixed ion environments. Under high Na+ ion concentration, as Mg2+ concentration increases, the ion neutralizing effect strengthens, weakening the driving force inside the nanopore, leading to longer translocation time. Conversely, at low Na+ concentration, an increase in Mg2+ concentration enhances the ion screening effect, aiding in faster translocation. Furthermore, these simulation results will be explained by quantitative analysis, advancing a deeper understanding of the complicated effects of the mixed Na+-Mg2+ ions.

Pulley Effect in the Capture of DNA Translocation through Solid-State Nanopores.

Nanopores are powerful single-molecule sensors for analyzing biomolecules such as DNA and proteins. Understanding the dynamics of DNA capture and translocation through nanopores is essential for optimizing their performance. In this study, we examine the effects of applied voltage and pore diameter on current blockage, translocation time, collision, and capture location by translocating λ-DNA through 5.7 and 16 nm solid-state nanopores. Ionic current changes are used to infer DNA conformations during translocation. We find that translocation time increases with pore diameter, which can be attributed to the decrease of the stall force. Linear and exponential decreases of collision frequency with voltage are observed in the 16 and 5.7 nm pores, respectively, indicating a free energy barrier in the small pore. Moreover, the results reveal a voltage-dependent bias in the capture location toward the DNA ends, which is explained by a "pulley effect" deforming the DNA as it approaches the pore. This study provides insights into the physics governing DNA capture and translocation, which can be useful for promoting single-file translocation to enhance nanopore sensing.

Nonmonotonic polymer translocation kinetics through nanopores under changing surface-polymer interactions.

Understanding the dynamics of polymers in confined environments is pivotal for diverse applications ranging from polymer upcycling to bioseparations. In this study, we develop an entropic barrier model using self-consistent field theory that considers the effect of attractive surface interactions, solvation, and confinement on polymer kinetics. In this model, we consider the translocation of a polymer from one cavity into a second cavity through a single-segment-width nanopore. We find that, for a polymer in a good solvent (i.e., excluded volume, u0 > 0), there is a nonmonotonic dependence of mean translocation time (τ) on surface interaction strength, ɛ. At low ɛ, excluded volume interactions lead to an energetic penalty and longer translocation times. As ɛ increases, the surface interactions counteract the energetic penalty imposed by excluded volume and the polymer translocates faster through the nanopore. However, as ɛ continues to increase, an adsorption transition occurs, which leads to significantly slower kinetics due to the penalty of desorption from the first cavity. The ɛ at which this adsorption transition occurs is a function of the excluded volume, with higher u0 leading to an adsorption transition at higher ɛ. Finally, we consider the effect of translocation across different size cavities. We find that the kinetics for translocation into a smaller cavity speeds up while translocation to a larger cavity slows down with increasing ɛ due to higher surface contact under stronger confinement.

Polymer translocation: Effects of confinement.

We investigate the influence of varying confinement on the dynamics of polymer translocation through a cone-shaped channel. For this, a linear polymer chain is modeled using self-avoiding walks on a square lattice. The cis side of a cone-shaped channel has a finite volume, while the trans side has a semi-infinite space. The confining environment is varied either by changing the position of the back wall while keeping the apex angle fixed or altering the apex angle while keeping the position of the back wall fixed. In both cases, the effective space ϕ, which represents the number of monomers in a chain relative to the total number of accessible sites within the cone, is reduced due to the imposed confinement. Consequently, the translocation dynamics are affected. We analyze the entropy of the confined system as a function of ϕ, which exhibits nonmonotonic behavior. We also calculate the free energy associated with the confinement as a function of a virtual coordinate for different positions of the back wall (base of the cone) along the conical axis for various apex angles. Employing the Fokker-Planck equation, we calculate the translocation time as a function of ϕ for different solvent conditions across the channel. Our findings indicate that the translocation time decreases as ϕ increases, but it eventually reaches a saturation point at a certain value of ϕ. Moreover, we highlight the possibility of controlling the translocation dynamics by manipulating the solvent quality across the channel. Furthermore, our investigation delves into the intricacies of polymer translocation through a cone-shaped channel, considering both repulsive and neutral interactions with the channel wall. This exploration unveils nuanced dynamics and sheds light on the factors that significantly impact translocation within confined channels.

Gain reversal in the translocation dynamics of a semiflexible polymer through a flickering pore

We study the driven translocation of a semiflexible polymer through an attractive extended pore with a periodically oscillating width. Similar to its flexible counterpart, a stiff polymer translocates through an oscillating pore more quickly than a static pore whose width is equal to the oscillating pore’s mean width. This efficiency quantified as a gain in the translocation time, highlights a considerable dependence of the translocation dynamics on the stiffness of the polymer and the attractive nature of the pore. The gain characteristics for various polymer stiffness exhibit a trend reversal when the stickiness of the pore is changed. The gain reduces with increasing stiffness for a lower attractive strength of the pore, whereas it increases with increasing stiffness for higher attractive strengths. Such a dependence leads to the possibility of a high degree of robust selectivity in the translocation process.

Translocation of a daughter vesicle in a model system of self-reproducing vesicles

Translocation of a daughter vesicle from a mother vesicle through a pore is experimentally studied by many groups using a model system of self-reproducing vesicles. However, the theoretical formulation of the problem is not fully understood. In the present study, we present a theoretical formulation of the process based on our previous work [P. Khunpetch et al., Phys. Fluids 33, 077103 (2021)]. In our previous work, we considered the daughter vesicle as a rigid body. In the present work, however, we allow the daughter vesicle to deform during the expulsion process. We thus derive the free energy constituting of the elastic moduli of both the mother and daughter vesicles, and of pressure-driven contribution. The minimum energy path of the translocation is searched by using the string method. With use of experimentally reasonable values of the elastic moduli, our improved model successfully reproduced the progress of the birthing process where there is no free energy barrier between the initial and the final states. The equations of motion of the daughter vesicle have been derived within the framework of the Onsager principle. We found that the translocation time of the daughter vesicle can be reduced when the pressure inside the mother vesicle increases, or the initial size of the daughter vesicle decreases.

Real-time monitoring of Ti(IV) metal ion binding of transferrin using a solid-state nanopore.

Transferrin, a central player in iron transport, has been recognized not only for its role in binding iron but also for its interaction with other metals, including titanium. This study employs solid-state nanopores to investigate the binding of titanium ions [Ti(IV)] to transferrin in a single-molecule and label-free manner. We demonstrate the novel application of solid-state nanopores for single-molecule discrimination between apo-transferrin (metal-free) and Ti(IV)-transferrin. Despite their similar sizes, Ti(IV)-transferrin exhibits a reduced current drop, attributed to differences in translocation times and filter characteristics. Single-molecule analysis reveals Ti(IV)-transferrin's enhanced stability and faster translocations due to its distinct conformational flexibility compared to apo-transferrin. Furthermore, our study showcases solid-state nanopores as real-time monitors of biochemical reactions, tracking the gradual conversion of apo-transferrin to Ti(IV)-transferrin upon the addition of titanium citrate. This work offers insights into Ti(IV) binding to transferrin, promising applications for single-molecule analysis and expanding our comprehension of metal-protein interactions at the molecular level.

Forced and spontaneous translocation dynamics of a semiflexible active polymer in two dimensions.

Polymer translocation is a fundamental topic in non-equilibrium physics and is crucially important to many biological processes in life. In the present work, we adopt two-dimensional Langevin dynamics simulations to study the forced and spontaneous translocation dynamics of an active filament. The influence of polymer stiffness on the underlying dynamics is explicitly analyzed. For the forced translocation, the results show a robust stiffness-induced inhibition, and the translocation time exhibits a dual-exponent scaling relationship with the bending modulus. Tension propagation (TP) is also examined, where we find prominent modifications in terms of both activity and stiffness. For spontaneous translocation into a pure solvent, the translocation time is almost independent of the polymer stiffness. However, when the polymer is translocated into a porous medium, an intriguing non-monotonic alteration of translocation time with increasing chain stiffness is demonstrated. The semiflexible chain is beneficial for translocation while the rigid chain is not conducive. Stiffness regulation on the diffusion dynamics of the polymer in porous media shows a consistent scenario. The interplay of activity, stiffness, and porous crowding provides a new mechanism for understanding the non-trivial translocation dynamics of an active filament in complex environments.

Adsorption of rare bases on transition metal doped γ-graphyne nanosheets: a DFT study.

Detection of rare bases (RBs) is key to understanding biological complexity, rapidly diagnosing genetic diseases and advancing personalized medicine. Electrochemical sensors are one of the most promising methods for RB detection, but their low responsiveness limits their effectiveness. Therefore, enhancing selectivity and sensitivity is necessary. γ-Graphyne (γ-GY) has garnered significant attention due to its sp2 and sp hybrid carbon bonds and layered two-dimensional planar structure, as well as its extensive conjugated system, and sizable triangular hole. In this study, the structural characteristics, electronic properties, and sensing parameters of the adsorption involving RBs with both γ-GY and transition metal (Fe, Co, and Ni)-doped γ-graphyne (TM-GY) nanosheets are investigated using density functional theory calculations to evaluate the potential of nanosheets for sequencing RBs in DNA. The result shows that the adsorption interaction between RBs and γ-GY is weak physical adsorption, making it difficult to distinguish RBs. In contrast, the adsorption of RBs with TM-GY is stronger chemisorption and can be completely separated by translocation time and sensing response. Through translocation time calculations, we demonstrate the high selectivity of Ni-GY for RBs. Furthermore, sensitivity analysis reveals that Fe-GY exhibits excellent responsiveness to RBs. Our work reveals that the TM-GY nanosheets hold promise for detecting RBs compared with the γ-GY, and may provide valuable insights for the design of graphyne-based biosensors and catalysts.

Exploring ssDNA translocation through α-hemolysin using coarse-grained steered molecular dynamics.

Protein nanopores have proven to be effective for single-molecule studies, particularly for single-stranded DNA (ssDNA) translocation. Previous experiments demonstrated their ability to distinguish differences in purine and pyrimidine bases and in the orientation of the ssDNA molecule inside nanopores. Unfortunately, the microscopic details of ssDNA translocation over experimental time scales, which are not accessible through all-atom molecular dynamics (MD), have yet to be examined. However, coarse-grained (CG) MD simulations enable systems to be simulated over longer characteristic times closer to experiments than all-atom MD. This paper studies ssDNA translocation through α-hemolysin nanopores exploiting steered MD using the MARTINI CG force field. The impacts of the sequence length, orientation inside the nanopore and DNA charges on translocation dynamics as well as the conformational dynamics of ssDNA during the translocation are explored. Our results highlight the efficacy of CG molecular dynamics in capturing the experimental properties of ssDNA translocation, including a wide distribution in translocation times per base. In particular, the phosphate charges of the DNA molecule are crucial in the translocation dynamics and impact the translocation rate. Additionally, the influence of the ssDNA molecule orientation on the translocation rate is explained by the conformational differences of ssDNA inside the nanopore during its translocation. Our study emphasizes the significance of obtaining sufficient statistics via CG MD, which can elucidate the great variety of translocation processes.