End-to-end attraction of duplex DNA

Recent experiments [Nakata, M. et al., End-to-end stacking and liquid crystal condensation of 6 to 20 basepair DNA duplexes. Science 2007; 318:1276–1279] have demonstrated spontaneous end-to-end association of short duplex DNA fragments into long rod-like structures. By means of extensive all-atom molecular dynamic simulations, we characterized end-to-end interactions of duplex DNA, quantitatively describing the forces, free energy and kinetics of the end-to-end association process. We found short DNA duplexes to spontaneously aggregate end-to-end when axially aligned in a small volume of monovalent electrolyte. It was observed that electrostatic repulsion of 5′-phosphoryl groups promoted the formation of aggregates in a conformation similar to the B-form DNA double helix. Application of an external force revealed that rupture of the end-to-end assembly occurs by the shearing of the terminal base pairs. The standard binding free energy and the kinetic rates of end-to-end association and dissociation processes were estimated using two complementary methods: umbrella sampling simulations of two DNA fragments and direct observation of the aggregation process in a system containing 458 DNA fragments. We found the end-to-end force to be short range, attractive, hydrophobic and only weakly dependent on the ion concentration. The relation between the stacking free energy and end-to-end attraction is discussed as well as possible roles of the end-to-end interaction in biological and nanotechnological systems

Tailoring Interleaflet Lipid Transfer with a DNA-based Synthetic Enzyme.

Lipid membranes, enveloping all living systems, are of crucial importance, and control over their structure and composition is a highly desirable functionality of artificial structures. However, the rational design of protein-inspired systems is still challenging. Here we have developed a highly functional nucleic acid construct that self-assembles and inserts into membranes, enabling lipid transfer between inner and outer leaflets. By designing the structure to account for interactions between the DNA, its hydrophobic modifications, and the lipids, we successfully exerted control over the rate of interleaflet lipid transfer induced by our DNA-based enzyme. Furthermore, we can regulate the level of lipid transfer by altering the concentration of divalent ions, similar to stimuli-responsive lipid-flipping proteins

Transport in one dimensional Coulomb gases: From ion channels to nanopores

We consider a class of systems where, due to the large mismatch of dielectric constants, the Coulomb interaction is approximately one-dimensional. Examples include ion channels in lipid membranes and water filled nanopores in silicon or cellulose acetate films. Charge transport across such systems possesses the activation behavior associated with the large electrostatic self-energy of a charge placed inside the channel. We show here that the activation barrier exhibits non-trivial dependence on the salt concentration in the surrounding water solution and on the length and radius of the channel.Comment: New references are have been added and discussed. 18 pages, 8 figure

Stretching and unzipping nucleic acid hairpins using a synthetic nanopore

We have explored the electromechanical properties of DNA by using an electric field to force single hairpin molecules to translocate through a synthetic pore in a silicon nitride membrane. We observe a threshold voltage for translocation of the hairpin through the pore that depends sensitively on the diameter and the secondary structure of the DNA. The threshold for a diameter 1.5 < d < 2.3 nm is V > 1.5 V, which corresponds to the force required to stretch the stem of the hairpin, according to molecular dynamics simulations. On the other hand, for 1.0 < d < 1.5 nm, the threshold voltage collapses to V < 0.5 V because the stem unzips with a lower force than required for stretching. The data indicate that a synthetic nanopore can be used like a molecular gate to discriminate between the secondary structures in DNA

Mesoscale simulations of surfactant dissolution and mesophase formation

The evolution of the contact zone between pure surfactant and solvent has been studied by mesoscale simulation. It is found that mesophase formation becomes diffusion controlled and follows the equilibrium phase diagram adiabatically almost as soon as individual mesophases can be identified, corresponding to times in real systems of order 10 microseconds.Comment: 4 pages, 2 figures, ReVTeX

Cations Regulate Membrane Attachment and Functionality of DNA Nanostructures.

The interplay between nucleic acids and lipids underpins several key processes in molecular biology, synthetic biotechnology, vaccine technology, and nanomedicine. These interactions are often electrostatic in nature, and much of their rich phenomenology remains unexplored in view of the chemical diversity of lipids, the heterogeneity of their phases, and the broad range of relevant solvent conditions. Here we unravel the electrostatic interactions between zwitterionic lipid membranes and DNA nanostructures in the presence of physiologically relevant cations, with the purpose of identifying new routes to program DNA-lipid complexation and membrane-active nanodevices. We demonstrate that this interplay is influenced by both the phase of the lipid membranes and the valency of the ions and observe divalent cation bridging between nucleic acids and gel-phase bilayers. Furthermore, even in the presence of hydrophobic modifications on the DNA, we find that cations are still required to enable DNA adhesion to liquid-phase membranes. We show that the latter mechanism can be exploited to control the degree of attachment of cholesterol-modified DNA nanostructures by modifying their overall hydrophobicity and charge. Besides their biological relevance, the interaction mechanisms we explored hold great practical potential in the design of biomimetic nanodevices, as we show by constructing an ion-regulated DNA-based synthetic enzyme

Ionic partition and transport in multi-ionic channels: A Molecular Dynamics Simulation study of the OmpF bacterial porin

We performed all-atom molecular dynamics simulations studying the partition of ions and the ionic current through the bacterial porin OmpF and two selected mutants. The study is motivated by new interesting experimental findings concerning their selectivity and conductance behaviour at neutral pH. The mutations considered here are designed to study the effect of removal of negative charges present in the constriction zone of the wild type OmpF channel (which contains on one side a cluster with three positive residues and on the other side two negatively charged residues). Our results show that these mutations induce an exclusion of cations from the constriction zone of the channel, substantially reducing the flow of cations. In fact, the partition of ions inside the mutant channels is strongly inhomogeneous, with regions containing excess of cations and regions containing excess of anions. Interestingly, the overall number of cations inside the channel is larger than the number of anions in the two mutants, as in the OmpF wild type channel. We found that the differences in ionic charge inside these channels are justified by the differences in electric charge between the wild type OmpF and the mutants, following an electroneutral balance

Cations Regulate Membrane Attachment and Functionality of DNA Nanostructures.

The interplay between nucleic acids and lipids underpins several key processes in molecular biology, synthetic biotechnology, vaccine technology, and nanomedicine. These interactions are often electrostatic in nature, and much of their rich phenomenology remains unexplored in view of the chemical diversity of lipids, the heterogeneity of their phases, and the broad range of relevant solvent conditions. Here we unravel the electrostatic interactions between zwitterionic lipid membranes and DNA nanostructures in the presence of physiologically relevant cations, with the purpose of identifying new routes to program DNA-lipid complexation and membrane-active nanodevices. We demonstrate that this interplay is influenced by both the phase of the lipid membranes and the valency of the ions and observe divalent cation bridging between nucleic acids and gel-phase bilayers. Furthermore, even in the presence of hydrophobic modifications on the DNA, we find that cations are still required to enable DNA adhesion to liquid-phase membranes. We show that the latter mechanism can be exploited to control the degree of attachment of cholesterol-modified DNA nanostructures by modifying their overall hydrophobicity and charge. Besides their biological relevance, the interaction mechanisms we explored hold great practical potential in the design of biomimetic nanodevices, as we show by constructing an ion-regulated DNA-based synthetic enzyme

Ionic conductivity, structural deformation, and programmable anisotropy of DNA origami in electric field.

The DNA origami technique can enable functionalization of inorganic structures for single-molecule electric current recordings. Experiments have shown that several layers of DNA molecules, a DNA origami plate, placed on top of a solid-state nanopore is permeable to ions. Here, we report a comprehensive characterization of the ionic conductivity of DNA origami plates by means of all-atom molecular dynamics (MD) simulations and nanocapillary electric current recordings. Using the MD method, we characterize the ionic conductivity of several origami constructs, revealing the local distribution of ions, the distribution of the electrostatic potential and contribution of different molecular species to the current. The simulations determine the dependence of the ionic conductivity on the applied voltage, the number of DNA layers, the nucleotide content and the lattice type of the plates. We demonstrate that increasing the concentration of Mg(2+) ions makes the origami plates more compact, reducing their conductivity. The conductance of a DNA origami plate on top of a solid-state nanopore is determined by the two competing effects: bending of the DNA origami plate that reduces the current and separation of the DNA origami layers that increases the current. The latter is produced by the electro-osmotic flow and is reversible at the time scale of a hundred nanoseconds. The conductance of a DNA origami object is found to depend on its orientation, reaching maximum when the electric field aligns with the direction of the DNA helices. Our work demonstrates feasibility of programming the electrical properties of a self-assembled nanoscale object using DNA.C.Y.L., J.Y. and A.A. were supported in part by the grants from the National Science Foundation (DMR-0955959, PHY-1430124 and ECC-1227034), and the National Institutes of Health (R01- HG007406). E.A.H. acknowledges support from Schweizerische Studienstiftung (Swiss Study Foundation) and Gonville & Caius College. S.H.A. acknowledges support from a Herchel Smith postdoctoral fellowship. J.K. acknowledges support from Chinese Scholarship Council and Cambridge Overseas Trust. UFK was supported by an ERC starting grant (PassMembrane, 261101). The authors gladly acknowledge supercomputer time provided through XSEDE Allocation Grant MCA05S028 and the Blue Waters Sustained Petascale Computer System (UIUC).This is the accepted manuscript. The final version is available from ACS at pubs.acs.org/doi/abs/10.1021/nn505825z