Interaction between DNAs on a Gold Surface - The Journal of Physical

The sequence of DNA is adapted from the recent work of Hill et al. ...... Heaven , M. W.; Dass , A.; White , P. S.; Holt , K. M.; Murray , R. W. J. Am...
0 downloads 0 Views 4MB Size
Download PDF
J. Phys. Chem. C 2009, 113, 15941–15947

15941

Interaction between DNAs on a Gold Surface One-Sun Lee and George C. Schatz* Department of Chemistry, Northwestern UniVersity, 2145 Sheridan Road, EVanston, Illinois 60208-3113 ReceiVed: June 10, 2009; ReVised Manuscript ReceiVed: July 22, 2009

Molecular dynamics (MD) methods have been used to study the conformation of DNA and its interaction with neighboring DNAs having the same base pair (bp) composition on a flat gold surface. Most of the simulations refer to a DNA that is surrounded by six other DNAs, with the initial distance between the DNAs chosen to be 27 Å to simulate high packing conditions. A six-carbon alkylthiolate linker connects each DNA to the gold surface, and there is an A10 spacer between the alkylthiolate and an 18 bp double-stranded (ds) region for each DNA. In addition, there is a 5 base dangling end on each DNA to match recent experiments in which the dangling ends appeared to show important interactions. We performed 20 ns MD simulations in water with high salt concentration, and it is found that the ds-DNA maintains Watson-Crick B-DNA conformations. The tilt angle (relative to the surface) of the central DNA in the cluster is 27° ( 5°, whereas the tilt angle of the surrounding DNAs is 11° ( 5°. The average angle between this middle ds-DNA and the surrounding ds-DNA is 25° ( 10° and the distance between DNAs is 37 ( 5 Å. These structural parameters arise because counterion-mediated osmotic effects cause the DNAs to move apart (the alkylthiolates always lie flat on the surface) and splay outward. The resulting DNA density is consistent with experiment for flat surfaces. However, in spite of this tendency for the DNAs to move apart, the dangling end of the middle DNA has close contact with its counterpart on one of the neighboring DNAs as a result of base stacking and non-Watson-Crick hydrogen bonding. This shows that DNA-DNA interactions not related to hybridization can stabilize closely packed aggregates of DNA-functionalized gold nanoparticles. We also find that the salt concentration around the middle DNA is increased by a factor of 2.3 relative to the bulk concentration. This increase corresponds to an increase in melting temperature of ∼14 K, which is consistent with our previous estimates of cooperative melting behavior. I. Introduction DNA-functionalized gold surfaces and nanoparticles have been used for a wide variety of applications including sequencing,1 drug discovery,2 and biosensing.3 Since the conformation of DNAs on surfaces and their interaction with neighboring DNAs significantly affect their properties,4 there have been many experimental and theoretical studies aimed at elucidating the DNA structures and thermodynamics. Barhoumi et al.5 studied the correlation of orientation and packing density of doublestranded DNA (ds-DNA) on a gold surface using surface-enhanced Raman spectroscopy (SERS). They found that ds-DNA tends to lie down on the surface for lower surface coverage. Wong and Pettitt6,7 reported molecular dynamics (MD) simulations of ds-DNA on a silica surface. Their simulations revealed that ds-DNA on the surface has both upright and tilted conformations. Yao et al.8 reported an optimum packing structure of single-stranded DNA (ss-DNA) and ds-DNA on gold surfaces using MD simulations. According to them, the optimum packing of ss-DNA is 0.19 DNA chain/nm2 whereas it is 58% of ss-DNA for ds-DNA. Even though these previous simulations revealed many aspects of the conformation of DNAs on gold surfaces, information about the interactions between neighboring DNAs has been incomplete. Only one strand of DNA was used in the simulation box per unit cell in these previous studies, so their analysis of interactions between neighboring DNAs is based on interactions between replicas. * Corresponding author: phone (847) 491-5657; fax (847) 491-7713; e-mail [email protected].

In this paper, we report atomistic MD simulations of the interactions between several DNA strands that are attached to a gold surface. This work is primarily motivated by recent experiments from the Mirkin lab,9-11 who studied the loading of DNA on gold nanopoarticles as a function of particle size (going from small particles to flat surfaces), and who demonstrated that DNA can link particles even when there are very few (1-4) base pairs available for hybridization such that duplex formation would not typically be thermally stable. In the Mirkin work, it was argued that “three-dimensional hybridization” provides additional stabilization to the short duplexes;10 however, a detailed structural model of this effect was not provided. In the present study, we consider seven ss-DNA strands that are attached to a [111] surface (ss-DNA in red in Figure 1) through alkylthioate linkers, -S(CH2)6-, with the strand centered in the middle surrounded by six other ss-DNA strands. The sequence (Figure 1a) is chosen to match recent experimental work11 in which particles functionalized with this sequence can link the particles together to form nanoparticle crystals. In this sequence, each ss-DNA has a 10-adenine spacer (region I). The surface coverage of DNA chemically adsorbed on a gold surface/ nanoparticle varies according to experimental conditions.5,9,11,12 We adopted a short initial distance between DNA strands to simulate a high packing density that is similar to what is found for DNA bound to small gold nanoparticles; however, the DNA is given some flexibility to define its own spacing through the alkylthiolate linker. A ss-DNA with complementary sequence to the adsorbed ss-DNA is introduced (ss-DNA in blue) to give a double-stranded DNA segment (region II). The introduced ss-DNA also has a 4-base dangling end sequence (region III).

10.1021/jp905469q CCC: $40.75  2009 American Chemical Society Published on Web 08/12/2009

15942

J. Phys. Chem. C, Vol. 113, No. 36, 2009

Lee and Schatz II. Computational Details

Figure 1. (a) Sequence of DNA used for the simulation. The alkylthiolate linker, -S(CH2)6-, is used for the connection between gold surface and DNA. (b) Side and (c) top views of the system. Region I is ss-DNA whereas region II is ds-DNA. Region III is a dangling end of ss-DNA. The distance between axes of DNAs is 27 Å.

We performed 20 ns MD simulations in water with high salt concentration, and the results show that the ds-DNA segment maintains a Watson-Crick B-DNA conformation during the simulations. In addition, the tilt angle of the middle ds-DNA is 27° ( 5° whereas the surrounding ds-DNAs are tilted by 11° ( 5°. The average angle between the middle ds-DNA and the surrounding ds-DNA is 25° ( 10° and their distance is 37 ( 5 Å, corresponding to DNAs that move apart from each other. We show that these structural effects can mostly be understood on the basis of counterion-mediated osmotic pressure effects. However, we also find that the dangling end of the middle DNA has close contact with a neighboring dangling end due to stacking and non-Watson-Crick hydrogen bonding, and this influences some structural parameters. These results provide insight concerning the three-dimensional model of Hurst et al.10 for the stability of aggregates formed from DNA-functionalized gold nanoparticles (DNA-Au NP). In addition, we show that the spacer ss-DNA in the middle strand has an extended conformation because of the high packing conditions. To assess the thermodynamic stability of the DNAs, the Na+ concentration around the middle DNA is scrutinized and it is found that this concentration is increased by a factor of 2.3 relative to the bulk concentration. Based on earlier studies of cooperative DNA melting effects, this corresponds to an increase in melting temperature of the DNA by ∼14 K. To the best of our knowledge, this is the first simulation that has determined the interaction between DNA strands on a gold surface at the atomistic level.

The gold surface is taken to have the dimensions 116 Å × 100 Å × 5 Å (three atoms thick) with a face-centered cubic structure. Seven ss-DNAs (5′-AAAAA AAAAA AAGAC GAATA TTTAA CAA-3′) are attached to the [111] gold surface via a six-carbon alkylthiolate linker (Figure 1). The sequence of DNA is adapted from the recent work of Hill et al.11 A complementary ss-DNA (3′-TTCTG CTTAT AAATT GTTAG CGC-5′) is attached to the ss-DNA bound to the gold surface. The initial helical parameters of the DNAs are adapted from the canonical B-DNA structure. The distance between the axes of the DNAs is taken to be 27 Å, corresponding to tightly packed DNA that has been found in recent nanoparticle experiments for high salt concentrations;9 however, the alkylthiolate linkers allow for dynamic determination of the optimized separations as we shall see. The starting structure of the DNA is developed by use of the x-leap module implemented in the AMBER package.13 The interactions between the gold atoms are described by Lennard-Jones potentials where the parameters (σ ) 2.569 Å and ε ) 0.458 eV) are taken from the literature.14 The force field parameters for the alkylthiolate are taken from the work of Hautman and Klein,15 while the parameters from CHARMm are used for DNA.16 The system was solvated in a water box by use of the SOLVATE17 module implemented in VMD.18 Periodic boundary conditions were used corresponding to a cubic box of dimensions of 120 × 102 × 146 Å3. Figure 1 shows the simulation box structure, and we note that the seven DNAs form a cluster that has little interaction with replica DNAs. This box was filled with 52 265 water molecules based on the modified TIP3P potential.19,20 To neutralize the system, 350 Na+ ions are added. In addition to these sodium ions, another 323 Na+ and Cl- ions are added to make the concentration of sodium ion be 0.62 M. Molecular dynamics simulations were carried out with NAMD2.21 A 1 ns molecular dynamics simulation at 400 K with a NVT ensemble was performed to equilibrate the system. During the equilibration, the position of the gold and DNA atoms is fixed with harmonic constraints. A second equilibration was performed with a NPT ensemble for 500 ps at 300 K. No constraint is applied during the second equilibration. In the production period, the system was simulated for 20 ns by use of the NPT ensemble and Langevin dynamics at a temperature of 300 K with a damping coefficient γ ) 5 ps-1.22 Pressure was maintained at 1 atm by the Langevin piston method with a piston period of 100 fs, a damping time constant of 50 fs, and piston temperature of 300 K.22,23 No atomic coordinates were constrained during the production period. Full electrostatics was employed using the particle-mesh Ewald method with 1 Å grid width.24 Nonbonded interactions were calculated with a group-based cutoff with a switching function and were updated every 5 time steps. Covalent bonds involving hydrogen were held rigid with the SHAKE algorithm,25 allowing a 2 fs time step. Atomic coordinates were saved every 10 ps for the trajectory analysis. III. Results and Discussion The conformation of the double helix of the middle DNA is monitored first. The root-mean-square deviation (rmsd) of the double helix part (region II in Figure 1) of the middle DNA is shown in Figure 2a. The canonical structure of B-DNA is used as a reference for calculation of the rmsd. Equation 1 is used

Interaction between DNAs on a Gold Surface

J. Phys. Chem. C, Vol. 113, No. 36, 2009 15943

Figure 3. Fluctuations of the tilt angle (θ) between the principal axis of ds-DNA and the surface normal axis. The tilt angle of the middle DNA is shown in red whereas all other tilt angles of surrounding DNAs are shown in black. Note that the red line increases after 10 ns. The average tilt angle of the middle DNA after 10 ns is 27° ( 5° whereas the average of tilt angle of the surrounding DNAs is 11° ( 5°. (Inset) Schematic definition of θ.

Figure 2. (a) Rmsd of ds-DNA located in the middle. The average rmsd during the 20 ns simulation is 2.4 ( 0.4 Å. The structure of dsDNA maintains a B-DNA conformation. (b) Snapshot of MD simulation at 20 ns. The middle strand is shown as a solid opaque model, whereas the other strands are shown as transparent models. The alkylthiolate linker, -S(CH2)6- (green), is laid flat on the gold surface.

for calculating the rmsd after translation and minimization of a given structure

[ ∑| M

rmsd(x, xcanon) )

1 x - xicanon M i)1 i

|]

1/2

2

(1)

relative to the reference structure, where xi and xicanon are the coordinates of the ith atom of DNA in the middle and the canonical B-DNA. M is the number of atoms in DNA excluding hydrogen atoms. The average value of the rmsd during the 20 ns simulation is 2.4 ( 0.4 Å. We find that the double helix of the middle DNA maintains the B-DNA conformation throughout this interval. Wong and Pettitt7 reported a molecular dynamics simulation of ds-DNA attached on silica surface through an epoxide-amine linker in 0.8 M NaCl solution. They also found that ds-DNA maintains the B-DNA conformer during a 40 ns simulation. Dong et al.26 reported the conformation of DNA adsorbed on a gold substrate using electrochemical ex situ SERS. They found that most DNA helices have B-form, but A-form DNA also exists. A snapshot of the system at 20 ns is shown in Figure 2b. The alkylthiolate linker that connects ss-DNA and gold nanoparticle is found to be laid flat on the gold surface. This is consistent with our previous simulation of ss-DNA-functionalized gold nanoparticle.27 In the simulation of Wong and Pettitt,6,7 the epoxide-amine linker remained in an extended conformation and away from the surface during the first 7 ns and finally collapsed on the surface also. In our simulation, the alkylthiolate linker laid down on the gold surface within the first 1 ns. The conformation of DNA on the gold surface is significantly affected by the structure of the linker that connects DNA and the gold surface. Sam et al.28 found that the thiol-derivatized

DNAs tethered through the 5′- linkage tend to lie at a 45° tilt angle, whereas 3′- tethered DNAs were almost lying on the gold surface. The tilt angle (θ) between the axis of ds-DNA and the z-axis that is perpendicular to the surface of gold is monitored during the simulation (Figure 3). The principal axis29 used is that for the ds-DNA segment. For the first 10 ns of simulation, all seven ds-DNAs have a tilt angle of 8° ( 4°. However, the middle DNA begins to lean to a neighboring DNA after 10 ns and tilts to 27° ( 5° (red line in Figure 3), whereas the surrounding DNAs are tilted by 11° ( 5° after 10 ns (black lines in Figure 3). In our simulation of ds-DNA adsorbed on a gold surface at a low surface coverage, the tilt angle is 7.3° ( 2.2°.30 Therefore, this would argue that only the middle DNA is in a high packing environment whereas the six surrounding DNAs are comparable to what is found for an isolated DNA strand. The tilt angle found in our simulation is smaller than the value reported by Wong and Pettitt.7 In their simulations, the tilt angle of ds-DNA fluctuates around 55° for the first 20 ns. After 20 ns, the ds-DNA began to reorient from the tilted position to an upright position and the tilt angle fluctuates between 0° and 30°. According to the study of Barhoumi et al.,5 the packing density of DNA significantly influences the tilt angle. They found that ds-DNA tends to have a smaller tilt angle at the high packing density (∼18 pmol/cm2) of DNA chemically adsorbed on a gold surface. Of course none of these earlier studies considered DNAs that have a dangling singlestranded portion, and none included more than one DNA in a unit cell. The angle between the principal axes of ds-DNAs (φ) and the distance between the center of mass of ds-DNAs (d) are shown in Figure 4. The angle, φ, and the distance, d, are defined between the middle DNA and one of the surrounding DNAs. Because of the six surrounding DNAs, six φ and d values are plotted versus simulation time. While the ds-DNAs are parallel for first few nanoseconds, the value of φ increases after 10 ns and the average value after 10 ns is 25° ( 10°. Since the earlier simulations of DNA strands chemically adsorbed on the surface contained only one strand in the simulation box, the analysis of interactions between neighboring DNA strands was performed only with replica images in the periodic cells. Therefore, the neighboring DNAs were always parallel in the previous simulations. However, the neighboring DNAs are not parallel in our simulation since we simulate six explicit neighboring DNAs. For the distance between neighboring ds-DNAs, the value of d also increases after 10 ns. The average value of d after 10 ns is

15944

J. Phys. Chem. C, Vol. 113, No. 36, 2009

Figure 4. (a) Fluctuation of the angle (φ) between the principal axes of ds-DNA. The angle, φ, is defined between the middle DNA and one of the surrounding DNA strands. The average value after 10 ns is 25° ( 10°. (b) Distance d from the center of mass of ds-DNA. The average distance after 10 ns is 37 ( 5 Å. (Insets) Schematic definitions of φ and d.

37 ( 5 Å even though it is 27 Å in the starting geometry. The standard deviation of the 37 Å result is relatively large as there is a significant range in d values in Figure 4 due to one exceptionally short value. This will be discussed below. Because of the higher charge density near the middle DNA, a higher counterion density occurs there (which we quantify later). This higher density leads to an effective osmotic pressure between the regions inside and outside the DNA cluster. The resulting in-flow of water molecules to this inner region drives the larger d values as well as the splaying of the DNAs. The experimentally determined surface coverage of DNA on a gold nanoparticle varies according to experimental conditions. According to the works of Hurst et al.9 and Hill et al.,11 the distance between ds-DNA that has a 10-adenine spacer chemically adsorbed on a gold nanoparticle varies from ∼26 to ∼39 Å depending on the particle diameter (10-250 nm). The distance between adsorbed DNAs becomes shorter for smaller gold nanoparticles due to splaying of the DNAs on the higher curvature particles as this decreases repulsions. The larger particle results are similar to what we find for flat gold surfaces. Yao et al.8 studied the packing structures of ss-DNA and dsDNA using MD simulations, and they found that the optimal packing densities are 0.19 DNA chains/nm2 for ss-DNA and 0.11 DNA chains/nm2 for ds-DNA. This value approximately corresponds to 26 (ss-DNA) and 34 Å (ds-DNA) for the interstrand distance. The ds-DNA distance is similar to what we find. We conclude that the average value of d (37 ( 5 Å) after 10 ns in our simulation is close to the optimum structure of ds-DNA. One of the extraordinary features of DNA-Au NPs is their high-temperature sharp melting profile. The sharp melting transition has been attributed to the high degree of cooperativity that exists between the DNA strands packed closely together on the surface of the gold nanoparticle.31,32 Recently, Hurst et al.10 reported that only one hybridizable base is needed to stabilize DNA-Au NP aggregates for 150 nm diameter gold nanoparticles. They proposed a three-dimensional hybridization

Lee and Schatz

Figure 5. (a) Top and (b) side views of trajectory associated with the last base of the middle strand during a 20 ns simulation are superimposed on the starting geometry of the system. The last cytosine base is shown as a blue sphere model and the trajectory is shown in red line. The last base of the middle DNA shows lateral fluctuations and has a close interaction with a neighboring strand.

model for the DNA-Au NP aggregates to explain the origin of the stability, which is in contrast to the one-dimensional structure for traditional DNA hybridization between two strands. According to their model, cumulative interactions between multiple pairs of adjacent strands lead to the sharp melting transition of DNA-Au NPs. Even though our model in this report does not explicitly describe the DNA-Au NP aggregates that were considered by Hurst et al., the behavior of the dangling end of DNA (region III in Figure 1) supports their three-dimensional hybridization model. The trajectory associated with the last cytosine base of the middle DNA is shown in Figure 5. The top and side views of this trajectory during the 20 ns simulation are superimposed on the starting geometry of the system. The last base of the middle DNA shows significant lateral fluctuations and has close interaction with one of the neighboring DNAs. This influences the 27° ( 5° tilt angle of the middle DNA that was mentioned earlier. In addition, Figure 4 (dark purple line) shows that the distance (d) between the middle DNA and the interacting DNA is 29.0 ( 1.5 Å, which is much shorter than the average value (37 ( 5 Å). To study the origin of this unusual DNA-DNA interaction, we examine the distance between the last cytosine base of the middle DNA and its counterpart in the interacting DNA. The results are shown in Figure 6a, where we use the centroid of the 6-membered ring of each base to define the distance. We see that the distance decreases during the first part of the trajectory, with the average distance after 10 ns being only 6.8 ( 2.4 Å. This distance is close enough to enable significant interactions (base stacking and hydrogen bonding) between bases, including bases on the adjacent strands. The normalized distribution of base-base distances for the end cytosines during the 20 ns simulation is shown in Figure 6b; this shows that ∼19% of the distribution belongs to base-base

Interaction between DNAs on a Gold Surface

J. Phys. Chem. C, Vol. 113, No. 36, 2009 15945

Figure 7. (a) Normalized distribution of the number of hydrogen bonding between dangling ends. The hydrogen bonding is counted between two -GCGC3′ dangling ends. (b) Snapshot of hydrogen bonding between dangling ends. The strand shown in blue is the middle strand, and the strand shown in red is one of the six surrounding strands.

Figure 6. (a) Fluctuations in the distance between interacting end cytosine bases. One base is from the middle DNA and the other base is from one of the surrounding DNAs. The centroid of the 6-membered ring of each cytosine base is used for the calculation. The average distance after 10 ns is 6.8 ( 2.4 Å. Compare with Figure 5. (b) Normalized distribution of base-base distance during 20 ns simulation. Approximately 19% of distribution belongs to base-base distances less than 5 Å. (c) Snapshot of the stacked bases of the end cytosines. The strand shown in blue is the middle strand, and the strand shown in red is one of the six surrounding strands. The 6-membered rings used for the definition of centroid are shown in the stick model.

distance less than 5 Å. As one example of these interactions, Figure 6c shows a snapshot of a structure that is clearly stacked. Hydrogen bonding between the two dangling -GCGC3′ ends is also monitored during the simulation. A cutoff distance of 3.9 Å between donor and acceptor and a donor-hydrogen-acceptor angle of 150-180° are used for the definition of hydrogen bonding. The normalized distribution of the number of hydrogen bonds is shown in Figure 7a. During the 20 ns simulation, hydrogen bonding is found in ∼35% of the saved structures. A snapshot of a hydrogen-bonded structure is shown in Figure 7b. The strand shown in blue at the left is from the middle strand, and the strand shown in red is from one of the six surrounding strands. Even though the cytosine-cytosine pair is not complementary, non-Watson-Crick hydrogen bonds are formed. Hydrogen bonding is found between many of the dangling bases and also between dangling bases and acceptors on the backbone. Now let us consider the lengths of the DNA strands. The conformation of the A10 linker (region I in Figure 1) has been studied by examining the azimuthal distance (Figure 8a) during the simulation. The tenth phosphorus atom is used to define the azimuthal distance, and it is clear from the figure that the azimuthal distance of the middle DNA is significantly larger

Figure 8. (a) Schematic representation of the azimuthal distance (z) of the tenth adenine base. (b) Snapshot of the system at 20 ns. The phosphorus atom of the tenth adenine of the middle DNA is shown in red sphere, whereas the others are shown in blue spheres. (c) Fluctuations in z with time. Average of the middle DNA after 10 ns is 46.8 ( 1.5 Å, and the average of the surrounding DNA is 34.8 ( 2.7 Å.

than that of the surrounding DNAs. As shown in Figure 8b,c, the azimuthal distance of the middle DNA is longer than that of the surrounding DNAs, with the average after 10 ns being

15946

J. Phys. Chem. C, Vol. 113, No. 36, 2009

Lee and Schatz

TABLE 1: Concentration of Sodium around the Middle DNAa region

sodium ion concentration (M)

melting temperature increase (K)

I II III

0.78 ( 0.11 1.46 ( 0.16 0.77 ( 0.15

3.6 13.5 3.4

a See Figure 1 for region assignment. The concentration of sodium ion in the bulk is 0.62 M. Equation 2 is used for calculation of the melting temperature increase.

46.8 ( 1.5 Å. The average azimuthal distance of the surrounding DNAs after 10 ns is 34.8 ( 2.7 Å. In our previous report of MD simulations of DNA-Au NP, the effective radius of DNAAu NP was found to be 2.2 Å/base for ss-DNA.27 However, here the ss-DNA in the middle DNA has an extended conformation (4.9 ( 0.1 Å/base for region I). For the surrounding ssDNAs, two to three bases are adsorbed on the gold surface and the remaining bases have an extended conformation. In our previous simulations, the ss-DNAs were symmetrically attached to a 1.8 nm diameter gold nanoparticle, and there was no significant interaction between the ss-DNAs. The middle DNA here, however, is in a highly packed environment and there are electrostatic and steric interactions with the neighboring DNAs as well as counterion-mediated effects. The surrounding DNAs are in a relatively low packed environment, so they adopt a less extended structure than the middle DNA. However, the surrounding DNAs are still more extended than the ss-DNAs adsorbed on a spherical particle in our previous report. Many of the unique properties of DNA-Au NPs can be related to the local salt concentration. According to the study of Jin et al.,33 aggregates of DNA-Au NPs provide an enhanced negative ion density (from phosphates) which leads to enhanced salt (i.e., Na+) concentration local to the DNA. This salt concentration also plays a crucial role for the intracellular stability of DNAAu NPs, making them useful for antisense studies, drug delivery, and intracellular molecular diagnostics. Recently, Seferos et al.34 found that the negatively charged surfaces of the DNA-Au NPs and resultant high local salt concentrations are responsible for enhanced stability to enzymatic degradation. In this report, we scrutinized the salt concentration around the middle DNA; the concentration of sodium ions around the middle DNA is presented in Table 1. The concentration is calculated from the number of sodium and water molecules that are within 15 Å of the middle DNA. We find that the sodium concentration varies according to location along the DNA strand. In the ss-DNA regions (regions I and III), the sodium concentration is about 0.8 M. This result is consistent with our previous simulations of ss-DNA attached on gold nanoparticle that reveals a 20% increase in sodium concentration around the DNA-Au NP. However, the sodium concentration is increased to 1.5 M in the double-helical region (region II). Since the negative charge of the double strand is twice that of the single strand, the concentration of sodium is higher around the double strand to compensate the negative charge. According to a previous study in our group,35 the relationship between melting temperature of DNA (in kelvins) and sodium concentration is

∆T ) -15.8 ln (C1 /C2)

(2)

where C1 is the bulk concentration of sodium and C2 is the concentration of sodium ions in the vicinity of DNA. The

increase in melting temperature of each region is also shown in Table 1. The increase in melting temperature of DNA around the double-helical region is about 13.5 K. This is consistent with our previous estimates35 for a DNA separation of 37 Å after we account for the fact that some of this enhancement would occur even for DNA strands that are infinitely separated. The infinite separation limit was examined in another paper,30 where we found that the sodium ion enhancement for isolated ds-DNA is a factor of 1.8, leading to an estimated temperature increase of 9 K. The difference between 13.5 and 9 K then matches the temperature estimate (∼8 K) for this separation made by Long et al.35 IV. Conclusion In this paper, we report MD simulations for a DNAfunctionalized gold surface at the atomistic level. The ds-DNA maintains a B-DNA conformation during the simulation, which is consistent with recent experimental and simulation results. The middle ds-DNA surrounded by other ds-DNAs is found to be tilted to the surface normal by 27° ( 5°, whereas the tilt angle of the surrounding DNAs is 11° ( 5°. The angle between ds-DNAs is 25° ( 10°, whereas the distance between them is 37 ( 5 Å. This separation distance is similar to estimates of this distance for ds-DNA on flat surfaces from earlier theory and experiment; however, what is unusual about this is that in spite of the large separation between ds-DNA, the dangling single strand at the end of the ds-DNA region is able to show strong interations with the single strand on another DNA. This result clarifies the picture provided in earlier work concerning the extra stability associated with interacting single strands on adjacent DNAs. We show that both base stacking and nonWatson-Crick hydrogen-bond formation are involved, but the structure is generally disordered and fluxional. Finally we found that the ss-DNA spacer composed of 10 adenines in the middle strand adopts an extended conformation whereas the surrounding ss-DNAs are less extended because they are partially adsorbed on the gold surface. Also, we found that the sodium concentration around the middle DNA is increased by a factor of 2.3 relative to the bulk concentration, which suggests that DNA-DNA interactions can lead to increased melting temperatures (cooperative melting effects) for these structures. Acknowledgment. This research was supported by the National Science Foundation (Grant CHE-0843832), by the NSEC Center at Northwestern (NSF Grant EEC-0647560), and by the Northwestern Center for Cancer Nanobiotechnology Excellence (1 U54 CA119341-01). References and Notes (1) Duggan, D. J.; Bittner, M.; Chen, Y.; Meltzer, P.; Trent, J. M. Nat. Genet. 1999, 21, 10. (2) Debouck, C.; Goodfellow, P. N. Nat. Genet. 1999, 21, 48. (3) Storhoff, J. J.; Elghanian, R.; Mucic, R. C.; Mirkin, C. A.; Letsinger, R. L. J. Am. Chem. Soc. 1998, 120, 1959. (4) McCullagh, M.; Prytkova, T.; Tonzani, S.; Winter, N. D.; Schatz, G. C. J. Phys. Chem. B 2008, 112, 10388. (5) Barhoumi, A.; Zhang, D.; Halas, N. J. J. Am. Chem. Soc. 2008, 130, 14040. (6) Wong, K.-Y.; Pettitt, B. M. Theor. Chem. Acc. 2001, 106, 233. (7) Wong, K.-Y.; Pettitt, B. M. Biopolymers 2003, 73, 570. (8) Yao, L.; Sullivan, J.; Hower, J.; He, Y.; Jiang, S. J. Chem. Phys. 2007, 127, 195101. (9) Hurst, S. J.; Lytton-Jean, A. K. R.; Mirkin, C. A. Anal. Chem. 2006, 78, 8313. (10) Hurst, S. J.; Hill, H. D.; Mirkin, C. A. J. Am. Chem. Soc. 2008, 130, 12192. (11) Hill, H. D.; Macfarlane, R. J.; Senesi, A. J.; Lee, B.; Park, S. Y.; Mirkin, C. A. Nano. Lett. 2008, 8, 2341.

Interaction between DNAs on a Gold Surface (12) Heaven, M. W.; Dass, A.; White, P. S.; Holt, K. M.; Murray, R. W. J. Am. Chem. Soc. 2008, 130, 3754. (13) Pearlman, D. A.; Case, D. A.; Caldwell, J. W.; Ross, W. S.; Cheatham, T. E.; Debolt, S.; Ferguson, D.; Seibel, G.; Kollman, P. Comput. Phys. Commun. 1995, 91, 1. (14) Agrawal, P. M.; Rice, B. M.; Thompson, D. L. Surf. Sci. 2002, 515, 21. (15) Hautman, J.; Klein, M. L. J. Chem. Phys. 1989, 91, 4994. (16) MacKerell, A. D.; Bashford, D.; Bellott, M.; Dunbrack, R. L.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; JosephMcCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher, W. E.; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M. J. Phys. Chem. B 1998, 102, 3586. (17) Grubmuller, H. SOLVATE, v1.2; Theoretical Biophysics Group, Institute for Medical Optics, Ludwig-Maximilian University, Munich, 1996. (18) Humphrey, W.; Dalke, A.; Schulten, K. J. Mol. Graph. 1996, 14, 33. (19) Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. J. Chem. Phys. 1983, 79, 926. (20) Mackerell, A. D.; Wiorkewiczkuczera, J.; Karplus, M. J. Am. Chem. Soc. 1995, 117, 11946. (21) Kale, L.; Skeel, R.; Bhandarkar, M.; Brunner, R.; Gursoy, A.; Krawetz, N.; Phillips, J.; Shinozaki, A.; Varadarajan, K.; Schulten, K. J. Comput. Phys. 1999, 151, 283.

J. Phys. Chem. C, Vol. 113, No. 36, 2009 15947 (22) Martyna, G. J.; Tobias, D. J.; Klein, M. L. J. Chem. Phys. 1994, 101, 4177. (23) Feller, S. E.; Zhang, Y. H.; Pastor, R. W.; Brooks, B. R. J. Chem. Phys. 1995, 103, 4613. (24) Darden, T.; York, D.; Pedersen, L. J. Chem. Phys. 1993, 98, 10089. (25) Andersen, H. C. J. Comput. Phys. 1983, 52, 24. (26) Dong, L. Q.; Zhou, J. Z.; Wu, L. L.; Dong, P.; Lin, Z. H. Chem. Phys. Lett. 2002, 354, 458. (27) Lee, O.-S.; Schatz, G. C. J. Phys. Chem. C 2009, 113, 2316. (28) Sam, M.; Boon, E. M.; Barton, J. K.; Hill, M. G.; Spain, E. M. Langmuir 2001, 17, 5727. (29) Taylor, J. R. Classical Mechanics; University Science Books: Sausalito, CA, 2005. (30) Lee, O.-S.; Schatz, G. C. MRS Proceedings; Materials Research Society: Warrendale, PA, 2009, (accepted for publication). (31) Elghanian, R.; Storhoff, J. J.; Mucic, R. C.; Letsinger, R. L.; Mirkin, C. A. Science 1997, 277, 1078. (32) Mirkin, C. A.; Letsinger, R. L.; Mucic, R. C.; Storhoff, J. J. Nature 1996, 382, 607. (33) Jin, R.; Wu, G.; Li, Z.; Mirkin, C. A.; Schatz, G. C. J. Am. Chem. Soc. 2003, 125, 1643. (34) Seferos, D. S.; Prigodich, A. E.; Giljohann, D. A.; Patel, P. C.; Mirkin, C. A. Nano Lett. 2009, 9, 308. (35) Long, H. L.; Kudlay, A. K.; Schatz, G. C. J. Phys. Chem. B 2006, 110, 2918.

JP905469Q