Supporting information for. DNA Origami-Graphene Hybrid Nanopore for DNA Detection

Transcription

1 Supporting information for DNA Origami-Graphene Hybrid Nanopore for DNA Detection Amir Barati Farimani, Payam Dibaeinia, Narayana R. Aluru Department of Mechanical Science and Engineering Beckman Institute for Advanced Science and Technology University of Illinois at Urbana-Champaign, Urbana, Illinois Corresponding Author, web: S-1

2 S.1 Calculations of conductivity Conductivity of the nanopores is calculated by using the electrical circuit depicted in Figure S1. In each system, solution and nanopore are modeled with two resistors connected in series. Since in all of our simulations an external electric field is applied in the z direction, the resistance or conductance is calculated in the z direction. The total resistance can be calculated as R t=r s+r n where R s is the resistance of the solution and R n is the resistance of the nanopore. The resistance of the solution is obtained as R s = σ L z A xy where σ stands for the resistivity of the buffer, L z is the length of the system in the z direction and A xy is the area of the water box in the x-y plane. In order to estimate the bulk resistivity σ, we performed five ionic current simulations with biases of 0.25 V, 0.5 V, 0.75 V, 1 V and 2 V for a 10.9 nm 11.9 nm 10.0 nm 1M NaCl solution cell. Figure S2 shows the current as a function of the applied bias. The bulk resistivity is then calculated as σ = r A xy L z E Z Y X Figure S1: Simulation system of a single layer DNA origami hybrid nanopore under an external electric field applied in the z direction. The equivalent electrical circuit consists of two resistors connected in series. In this case, R s and R n denote the resistivity of the solution and single layer DNA origami hybrid nanopore, respectively. Resistivity of the nanopore R n depends on the number of layer(s) of DNA origami nanoplate and the resistivity of the graphene sheet. S-2

3 Ionic current (na) Bias (V) Figure S2: Current versus applied bias (I-V curve) for the ionic current simulations of the 1M NaCl solution cell. where r is the reciprocal of the slope of the I-V curve corresponding to the simulated cell (Figure S2), A xy and L z denote the area of the cell in the x-y plane and its length in the z direction, respectively. Based on our calculations, resistivity of the buffer is σ = 0.18 Ωm (using r = MΩ, A xy = nm 2 and L z = 10.0 nm). Since the dimensions of the simulated cell and the solution box are the same, we obtain R s = r = MΩ. The resistance of the nanopore depends on the number of layers of DNA origami nanoplate used in the structure. It should be noted that in each case, all the resistors are connected in series. So, the most resistive structure is the double layer DNA origami hybrid nanopore and its resistance can be calculated as: R t = 2R d + R g + R s where R d is the resistance of a single layer DNA origami nanopore (just account for the currents through the middle pore and not the leakage current), R g is the resistance of the graphene nanopore and R s is the solution resistivity. Here, we simply consider R t as the reciprocal of the slope of the IV curve corresponding to the double layer DNA origami hybrid nanopore, which is modeled by the slope of the linear fit to the simulation data. The, conductivity G is then defined as the inverse of the resistance S-3

4 G = 1 R Table S1 shows the calculated conductance for different nanopores. Nanopore Conductance (ns) Double layer DNA origami hybrid Single layer DNA origami hybrid Single layer DNA origami Graphene Table S1: The conductance of various nanopores considered in this study. S.2 DNA origami design Because of some restrictions in converting cadnano 1 files to NAMD 2 input files, we made two additional break points in the scaffold strand of the DNA origami nanoplate. These additional break points are used to sequence the scaffold strand in such a way to create more T bases at the location of the pore. The single layer DNA origami pore was created by deleting eight A bases of staple strands in the middle of the nanoplate. The additional break points were connected again to have a single scaffold strand after the pore was created. Figure S3 illustrates the connectivity map and the sequence of bases of the single layer DNA origami nanoplate used in our simulations. Figure S3: Connectivity map of the single layer DNA origami nanoplate. The additional break points at the middle of the nanoplate were generated to accumulate more T bases in the scaffold strand at the location of the pore. These break points were connected again to have a single scaffold strand before starting the simulations. S-4

5 By following the same procedure, we made four additional break points to sequence the scaffold strand of the double layer DNA origami nanoplate. We placed eight T bases on the first layer and ten T bases on the second layer of the double layer DNA origami nanoplate around the pore. The DNA origami pore was created by deleting eighteen A bases of staple strands in the middle of the nanoplate (Figure S4a). The additional break points were connected again to have a single scaffold strand after the pore was created. Figure S4a shows the sequence of the bases and Figure S4b shows the connectivity map of the scaffold strand of the double layer DNA origami nanopore. a b Figure S4: a Sequence of the bases of scaffold and staple strands of the double layer DNA origami nanoplate. The additional break points at the middle of the nanoplate were generated to assign appropriate base types to the DNA origami nanoplate and place more T bases in the scaffold strand at the location of the pore. These break points were connected again to have a single scaffold strand before starting the simulations. b Final connectivity map of the scaffold and staple strands of the double layer DNA origami nanoplate after reconnecting the break points. S-5

6 S.3 Density of bases around the pore mouth Density of bases around the pore for different nucleotide translocation is shown in Figure S5. a b Number of bases around the pore A C G T Number of bases around the pore A C G T c Number of bases around the pore A C G T Figure S5: Number of different bases of DNA origami nanoplate in a cylindrical region with a radius of 22.4 Å centered with the pore for the translocation of a Poly(dC) 20 b Poly(dG) 20 c Poly(dT) 20 though single layer DNA origami hybrid nanopore. In all simulations, more A bases reside around the pore than the other base types. The small amplitude fluctuations of the number of bases indicate that the DNA origami nanoplate is stable on top of the graphene nanopore during the simulation time. S.4 Motion of DNA origami on top of graphene under external biases DNA origami has a negative net charge and interacts with the external electric field. Negative biases apply forces to DNA origami in the positive z direction. Strong enough negative biases should theoretically make S-6

7 DNA origami to move away from the graphene sheet. We have monitored the distance of DNA origami atoms from the graphene sheet under both positive and negative biases. In Figure S6a we compared the averaged (over all the atoms) distance of DNA origami from graphene under small biases over the whole simulation time. Under a small negative bias of 0.5V, the averaged distance of DNA origami from graphene is slightly larger than that under the small positive bias of 0.5V. To see the effect of larger biases, we averaged the distance of DNA atoms from graphene over all the atoms and during the entire simulation time for different external biases. Figure S6b suggests that for biases larger (in magnitude) than -1V, the average distance of DNA origami from graphene is considerably large since the external force applied by the electric field overcomes the interactions (stickiness) between the DNA origami and graphene. Under large negative biases, the interaction between the DNA origami and the external field increases the motion of DNA origami on top of graphene while the stickiness of DNA origami to graphene under smaller biases keeps DNA origami from large motions. We computed the Root Mean Square Deviations (RMSD) of the DNA origami with respect to its initial equilibrated position on top of graphene under different small and large external biases. Figure S6c shows that the interaction between DNA origami and high negative external fields cause DNA origami to have more displacement on top of graphene, while positive biases (at least biases lower than 2V) do not significantly increase the motion of DNA origami compared to the equilibrium state. S-7

8 a Average distance (Å) V -0.5 V b Distance origami to graphene (Å) Applied bias (V) c RMSD (Å) V -0.5 V 0.0 V 2.0 V -2.0 V Figure S6: a The distance of DNA origami from the graphene nanopore along the z direction averaged over all the atoms of the DNA origami nanopore. An external bias of positive and negative 0.5 V was applied. b The distance of the DNA origami nanopore from the graphene nanopore in the z direction, averaged over the entire simulations times and over all the atoms of the DNA origami under various external biases. c Root Mean Squared Deviations (RMSD) of the DNA origami on top of the graphene nanopore under small and large external biases. S.5 Sandwiched DNA origami-graphene hybrid nanopore In order to prevent the detachment of DNA origami from graphene under negative external biases, we suggest a new hybrid nanopore consisting of a DNA origami nanopore sandwiched between two graphene sheets with nanopores (Figure S7a). Although the fabrication of this hybrid structure is intriguing, it offers benefits for controlling the translocation rate. We characterized the I-V curve of the sandwiched DNA origami nanopore solvated in an aqueous 1M NaCl solution under positive and negative external biases S-8

9 (Figure S7b). Figure S7b shows that sandwiched DNA origami is more resistive, as evidenced by the lower ionic current, compared to the single layer DNA origami graphene hybrid nanopore. a b Ionic Current (na) Graphene+origami Sandwiched origami Bias (V) Figure S7: a Simulation system of the DNA origami nanopore sandwiched between two graphene nanopores and solvated in an aqueous 1M NaCl solution. b A comparison of IV curves of the sandwiched DNA origami graphene and single layer DNA origami hybrid nanopores. S.6 I-V curve of the hybrid nanopore solvated in 1M KCl aqueous solution In order to realize the effect of the buffer and understand how the results may change due to the buffer considered, we repeated our ionic current simulations for the single layer DNA origami hybrid nanopore solvated in an aqueous 1M KCl solution. We characterized the current through the hybrid nanopore under different biases and compared them with the results of 1M NaCl solution. Figure S8 shows that under the same bias, the current of KCl ions through the single layer DNA origami graphene hybrid nanopore is relatively higher than the current of NaCl ions. Higher conductance of the hybrid DNA origami graphene nanopore in a KCl solution suggests that KCl can be a better electrolyte as the signal is higher while the signal-to-noise ratio still should be carefully studied. S-9

10 Ion Current (na) M KCl 1M NaCl Bias (V) Figure S8: I-V curves for the single layer DNA origami hybrid nanopore solvated in two different buffer solutions of KCl and NaCl ions. Lines are linear fits with the corresponding color for the symbols. S.7 I-V Interactions between ssdna and hybrid nanopore The nonhybridized dangling bases of the hybrid nanopore effectively interact with bases of poly(da) that yield long dwell times for A bases inside the nanopore. However, the residence times of the other base types especially the long dwell time of C bases compared to the G and T bases is explained by the overall interactions between ssdnas and nanopore and instantaneous hydrogen bonding between ssdna and hybridized bases pairs near the nanopore. Long residence time of A bases inside the nanopore is expected due to the effective interactions with dangling bases, but in order to explain the residence time of other bases we characterized the z component of VDW and electrostatic forces acting on ssdna inside the nanopore. Figure S9 shows that large forces act on the ssdna in the nanopore in the negative z direction during the translocation of poly(dg) and poly(dt), while these forces are much smaller during the translocation of poly(dc). Large forces in the negative z direction push G and T bases to quickly move through the nanopore and that reduces their residence time. However, C bases can reside in the nanopore for longer times due to the smaller forces acting on them in the negative z direction. We also characterized the instantaneous hydrogen bonding between ssdnas and hybridized bases of the DNA origami. Figure S10 shows the number of hydrogen bonds between poly(dc) and G bases, poly(dg) and C bases and S-10

11 between poly(dt) and A bases of the hybridized base pairs of the DNA origami near the nanopore. This figure shows that poly(dc) has considerable HB interactions with the G bases of the G-C base pairs of the DNA origami near the nanopore that can give rise to higher residence time of poly(dc), while the G and T bases form fewer hydrogen bonds with C and A bases, respectively, of the DNA origami near the pore. The higher number of hydrogen bonds between poly(dc) and the DNA origami finds its root in the abundance of G bases (G-C base pairs) in the DNA origami near the pore. a b F z (Kcal/mol Å) VDW Electrostatic Total F z (Kcal/mol Å) VDW Electrostatic Total c VDW Electrostatic Total F z (Kcal/mol Å) Figure S9: z component of VDW and electrostatics forces applying on a poly(dc), b poly(dg) and c poly(dt) from nanopore. Lighter red and blue colors are corresponded to the original forces that have been recorded from simulations and darker ones are corresponded to the block averaged data. Yellow plot shows the block averaged total force applying on ssdna from nanopore in z direction. S-11

12 a b Hydrogen bonds (#) Hydrogen bonds (#) c 1.0 Hydrogen bonds (#) Figure S10: a Number of hydrogen bonds formed between bases of poly(dc) and G bases of the G-C base pairs near the pore. b Number of hydrogen bonds formed between bases of poly(dg) and C bases of the C-G base pairs near the pore. c Number of hydrogen bonds formed between bases of poly(dt) and A bases of the A-T base pairs near the pore. S-12

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