Stochastic Resonance Behavior of DNA Translocation with an Oscillatory Electric Field

Stochastic resonance (SR) describes the synchronization between noise of a system and an applied oscillating field to achieve an optimized response signal. In this work, we use simulations to investigate the phenomenon of SR of a single stranded DNA driven through a nanopore when an oscillating electric field is added. The system is comprised of a MspA protein nanopore embedded in a membrane and different lengths of DNA is driven from one end of the pore to the other via a constant potential difference. We superimposed an oscillating electric field on top of the existing electric field. The source of noise is due to thermal fluctuations, since the system is immersed in solution at room temperature. Here, the signal optimization we seek is the increase in translocation time of DNA through the protein nanopore. Normally, translocation time scales linearly with DNA length and inversely with driving force in a drift dominanted regime. We found a non monotonic dependence of the mean translocation time with the frequency of the oscillating field. This non-monotonic behavior of the translocation time is observed for all lengths of DNA, but SR occurs only for longer DNA. Furthermore, we also see evidence of DNA extension being influenced by the oscillating field while moving through the nanopore.

Translocation through a narrow pore under a pulling force

We employ a three-dimensional molecular dynamics to simulate a driven polymer translocation through a nanopore by applying an external force, for four pore diameters and two external forces. To see the polymer and pore interaction effects on translocation time, we studied nine interaction energies. Moreover, to better understand the simulation results, we investigate polymer center of mass, shape factor and the monomer spatial distribution through the translocation process. Our results reveal that increasing the polymer-pore interaction energy is accompanied by an increase in the translocation time and decrease in the process rate. Furthermore, for pores with greater diameter, the translocation becomes faster. The shape analysis of the polymer indicates that the polymer shape is highly sensitive to the interaction energy. In great interactions, the monomers come close to the pore from both sides. As a result, the translocation becomes fast at first and slows down at last. Overall, it can be concluded that the external force does not play a major role in the shape and distribution of translocated monomers. However, the interaction energy between monomer and nanopore has a major effect especially on the distribution of translocated monomers on the trans side.

Polymer translocation of linear polymer and ring polymer influenced by crowding

The transport of biomolecules across bio-membranes occurs in a complex environment where the fluid on both sides of the membrane contains many inclusions. The Monte Carlo method and the hard-sphere (HS) model are used to simulate the translocation of linear polymer and ring polymer through a nanopore in a crowded environment. We compare the results of linear polymer and ring polymer and find that the ring polymer is more sensitive to the surrounding environment. Moreover, the influences of the nanopore and the inclusions to the translocation are studied and our results show that the nanopore changes the translocation time and the inclusions change the translocation tendency to the random side of the membrane. Here, the radius of gyration is described as a balance.

Theoretical Modeling of Polymer Translocation: From the Electrohydrodynamics of Short Polymers to the Fluctuating Long Polymers

The theoretical formulation of driven polymer translocation through nanopores is complicated by the combination of the pore electrohydrodynamics and the nonequilibrium polymer dynamics originating from the conformational polymer fluctuations. In this review, we discuss the modeling of polymer translocation in the distinct regimes of short and long polymers where these two effects decouple. For the case of short polymers where polymer fluctuations are negligible, we present a stiff polymer model including the details of the electrohydrodynamic forces on the translocating molecule. We first show that the electrohydrodynamic theory can accurately characterize the hydrostatic pressure dependence of the polymer translocation velocity and time in pressure-voltage-driven polymer trapping experiments. Then, we discuss the electrostatic correlation mechanisms responsible for the experimentally observed DNA mobility inversion by added multivalent cations in solid-state pores, and the rapid growth of polymer capture rates by added monovalent salt in α -Hemolysin pores. In the opposite regime of long polymers where polymer fluctuations prevail, we review the iso-flux tension propagation (IFTP) theory, which can characterize the translocation dynamics at the level of single segments. The IFTP theory is valid for a variety of polymer translocation and pulling scenarios. We discuss the predictions of the theory for fully flexible and rodlike pore-driven and end-pulled translocation scenarios, where exact analytic results can be derived for the scaling of the translocation time with chain length and driving force.

Dielectric Trapping of Biopolymers Translocating through Insulating Membranes

Sensitive sequencing of biopolymers by nanopore-based translocation techniques requires an extension of the time spent by the molecule in the pore. We develop an electrostatic theory of polymer translocation to show that the translocation time can be extended via the dielectric trapping of the polymer. In dilute salt conditions, the dielectric contrast between the low permittivity membrane and large permittivity solvent gives rise to attractive interactions between the c i s and t r a n s portions of the polymer. This self-attraction acts as a dielectric trap that can enhance the translocation time by orders of magnitude. We also find that electrostatic interactions result in the piecewise scaling of the translocation time τ with the polymer length L. In the short polymer regime L ≲ 10 nm where the external drift force dominates electrostatic polymer interactions, the translocation is characterized by the drift behavior τ ∼ L 2 . In the intermediate length regime 10 nm ≲ L ≲ κ b − 1 where κ b is the Debye–Hückel screening parameter, the dielectric trap takes over the drift force. As a result, increasing polymer length leads to quasi-exponential growth of the translocation time. Finally, in the regime of long polymers L ≳ κ b − 1 where salt screening leads to the saturation of the dielectric trap, the translocation time grows linearly as τ ∼ L . This strong departure from the drift behavior highlights the essential role played by electrostatic interactions in polymer translocation.

Translocation of Charged Polymers through a Nanopore in Monovalent and Divalent Salt Solutions: A Scaling Study Exploring over the Entire Driving Force Regimes

Langevin dynamics simulations are performed to study polyelectrolytes driven through a nanopore in monovalent and divalent salt solutions. The driving electric field E is applied inside the pore, and the strength is varied to cover the four characteristic force regimes depicted by a rederived scaling theory, namely the unbiased (UB) regime, the weakly-driven (WD) regime, the strongly-driven trumpet (SD(T)) regime and the strongly-driven isoflux (SD(I)) regime. By changing the chain length N, the mean translocation time is studied under the scaling form ⟨ τ ⟩ ∼ N α E − δ . The exponents α and δ are calculated in each force regime for the two studied salt cases. Both of them are found to vary with E and N and, hence, are not universal in the parameter’s space. We further investigate the diffusion behavior of translocation. The subdiffusion exponent γ p is extracted. The three essential exponents ν s , q, z p are then obtained from the simulations. Together with γ p , the validness of the scaling theory is verified. Through a comparison with experiments, the location of a usual experimental condition on the scaling plot is pinpointed.

Computer simulation of knotted proteins unfold and translocation through nano-pores

We study the unfold and translocation of knotted protein, YibK and YbeA, through α-hemolysin nano-pore via a coarse grained computational model. We observe that knot of protein unfold in advance before the translocation take place. We also characterized the translocation mechanism by studying the thermodynamical and kinetic properties of the process. In particular, we study the average of translocation time, and the translocation probability as a function of pulling force F acting in the channel. In limit of low pulling inward constant force acting along the axis of the pore, the YibK knotted protein takes longer average translocation time as compare to YbeA knotted protein.