Signature properties of water: Their molecular electronic origins.

Water challenges our fundamental understanding of emergent materials properties from a molecular perspective. It exhibits a uniquely rich phenomenology including dramatic variations in behavior over the wide temperature range of the liquid into water's crystalline phases and amorphous states. We show that many-body responses arising from water's electronic structure are essential mechanisms harnessed by the molecule to encode for the distinguishing features of its condensed states. We treat the complete set of these many-body responses nonperturbatively within a coarse-grained electronic structure derived exclusively from single-molecule properties. Such a "strong coupling" approach generates interaction terms of all symmetries to all orders, thereby enabling unique transferability to diverse local environments such as those encountered along the coexistence curve. The symmetries of local motifs that can potentially emerge are not known a priori. Consequently, electronic responses unfiltered by artificial truncation are then required to embody the terms that tip the balance to the correct set of structures. Therefore, our fully responsive molecular model produces, a simple, accurate, and intuitive picture of water's complexity and its molecular origin, predicting water's signature physical properties from ice, through liquid-vapor coexistence, to the critical point.

Nanoscale imaging reveals laterally expanding antimicrobial pores in lipid bilayers.

Antimicrobial peptides are postulated to disrupt microbial phospholipid membranes. The prevailing molecular model is based on the formation of stable or transient pores although the direct observation of the fundamental processes is lacking. By combining rational peptide design with topographical (atomic force microscopy) and chemical (nanoscale secondary ion mass spectrometry) imaging on the same samples, we show that pores formed by antimicrobial peptides in supported lipid bilayers are not necessarily limited to a particular diameter, nor they are transient, but can expand laterally at the nano-to-micrometer scale to the point of complete membrane disintegration. The results offer a mechanistic basis for membrane poration as a generic physicochemical process of cooperative and continuous peptide recruitment in the available phospholipid matrix.

Phase diagram of cuprate high-temperature superconductors described by a field theory based on anharmonic oxygen degrees of freedom.

In high temperature superconductors, although some phenomena such as the Mott transition (MT) at low doping are clearly driven by electron correlations, recent experimental data imply that anharmonic oxygen degrees of freedom-characteristic of perovskite materials-are playing a significant role. A key test of the role of anharmonic oxygen is to reproduce the complex cuprate phase diagram from a simple model. Here, we show that a field theory based on nonlinear coupling to anharmonic oxygens, parametrized from ab initio calculations, quantitatively reproduces the cuprate phase diagram for dopings above the MT. Pairing is mediated by renormalized oxygen vibrations transmuted into excitations of the pseudogap. The observed strong dependence of gap to transition temperature ratio on Tc also emerges from this field theory. This work suggests that including vibrational degrees of freedom is key to developing a complete understanding of the cuprates.

First realization of the piezoelectronic stress-based transduction device.

We present the first realization of a monolithically integrated piezoelectronic transistor (PET), a new transduction-based computer switch which could potentially operate conventional computer logic at 1/50 the power requirements of current Si-based transistors (Chen 2014 Proc. IEEE ICICDT pp 1-4; Mamaluy et al 2014 Proc. IWCE pp 1-2). In PET operation, an input gate voltage expands a piezoelectric element (PE), transducing the input into a pressure pulse which compresses a piezoresistive element (PR). The PR resistance goes down, transducing the signal back to voltage and turning the switch 'on'. This transduction physics, in principle, allows fast, low-voltage operation. In this work, we address the processing challenges of integrating chemically incompatible PR and PE materials together within a surrounding cage against which the PR can be compressed. This proof-of-concept demonstration of a fully integrated, stand-alone PET device is a key step in the development path toward a fast, low-power very large scale integration technology.

Hydrogen bonding and molecular orientation at the liquid-vapour interface of water.

We determine the molecular structure and orientation at the liquid-vapour interface of water using an electronically coarse grained model constructed to include all long-range electronic responses within Gaussian statistics. The model, fit to the properties of the isolated monomer and dimer, is sufficiently responsive to generate the temperature dependence of the surface tension from ambient conditions to the critical point. Acceptor hydrogen bonds are shown to be preferentially truncated at the free surface under ambient conditions and a related asymmetry in hydrogen bonding preference is identified in bulk water. We speculate that this bonding asymmetry in bulk water is the microscopic origin of the observed surface structure.

Antibody recognition of a human chorionic gonadotropin epitope (hCGbeta66-80) depends on local structure retained in the free peptide.

Human chorionic gonadotropin (hCG) is an important biomarker in pregnancy and oncology, where it is routinely detected and quantified by specific immunoassays. Intelligent epitope selection is essential to achieving the required assay performance. We present binding affinity measurements demonstrating that a typical ß3-loop-specific monoclonal antibody (8G5) is highly selective in competitive immunoassays and distinguishes between hCGß(66-80) and the closely related luteinizing hormone (LH) fragment LHß(86-100), which differ only by a single amino acid residue. A combination of optical spectroscopic measurements and atomistic computer simulations on these free peptides reveals differences in turn type stabilized by specific hydrogen bonding motifs. We propose that these structural differences are the basis for the observed selectivity in the full protein.

Evidence for electronic gap-driven metal-semiconductor transition in phase-change materials.

Phase-change materials are functionally important materials that can be thermally interconverted between metallic (crystalline) and semiconducting (amorphous) phases on a very short time scale. Although the interconversion appears to involve a change in local atomic coordination numbers, the electronic basis for this process is still unclear. Here, we demonstrate that in a nearly vacancy-free binary GeSb system where we can drive the phase change both thermally and, as we discover, by pressure, the transformation into the amorphous phase is electronic in origin. Correlations between conductivity, total system energy, and local atomic coordination revealed by experiments and long time ab initio simulations show that the structural reorganization into the amorphous state is driven by opening of an energy gap in the electronic density of states. The electronic driving force behind the phase change has the potential to change the interconversion paradigm in this material class.

Conductance through multilayer graphene films.

The ballistic conductance through junctions between multilayer graphene films and several different metals is studied using ab initio calculations within the local density approximation. The system consists of films of up to four graphene layers (Bernal stacking) between metallic electrodes, assuming reasonable metal-graphene epitaxial relationships. For some metals, the conductance decays exponentially with increasing number of layers, while for others the conductance saturates with film thickness. This difference in asymptotic behavior stems from the crystal momentum (mis)match between the bulk Fermi-level states in the electrode and those in the film. In contrast, for sufficiently thin films the bonding between the metal and the adjacent graphene layer dominates, giving a metal dependence for graphene similar to that seen experimentally for single-wall carbon nanotubes. Among the metals considered here, we find Pd to be the best for electrodes to films with up to 4 graphene layers.

Nonlinear screening in multilayer graphene systems.

Electrostatic screening in multilayer graphene is highly nonlinear due to the vanishing density of states at the Fermi level. Using a discrete model we study the charge screening normal to the layers. Our model shows a strong charge and temperature dependence and has a simple continuum limit at T=0 for undoped systems. Doped systems can exhibit more complex behavior due to minority-carrier screening. Most importantly we find that the screening length can vary more than an order of magnitude depending on the experimental conditions, reconciling the large range of screening lengths reported in previous experiments. This has important consequences for technological applications of multilayer graphene used in electrodes or transistor channels.

Autonomous folding in the membrane proximal HIV peptide gp41(659-671): pH tuneability at micelle interfaces.

The flexibility of the Membrane Proximal Region (MPR) of the HIV-1 gp41 envelope glycoprotein is believed to be relevant to its biological function. Its conformational bias is potentially influenced by the various environmental conditions experienced during viral fusion. Using a combination of Circular Dichroism and Molecular Dynamics simulations, we show that a very short MPR fragment gp41(659-671) spanning the 2F5 monoclonal antibody epitope, exhibits autonomous helical folding in the presence of membrane mimicking SDS micelles and the extent of which can be tuned by pH variation: Specifically, the peptide shows no defined fold type at basic pH but is helical at physiological and lower pH environments. By contrast, no such control of helical folding by pH is observed in aqueous solutions in the absence of SDS. Instead, the experimental data imply that unfolded structures persist and that pH has negligible influence on conformational bias. We also explore the pronounced sensitivity to standard empirical potentials and conclude that AMBER-ff03 provides a reasonably accurate description of the solution state structure and is therefore a good choice for future exploration of membrane-induced phenomena.

Electrochemical characterization of thin film electrodes toward developing a DNA transistor.

The DNA-Transistor is a device designed to control the translocation of single-stranded DNA through a solid-state nanopore. Functionality of the device is enabled by three electrodes exposed to the DNA-containing electrolyte solution within the pore and the application of a dynamic electrostatic potential well between the electrodes to temporarily trap a DNA molecule. Optimizing the surface chemistry and electrochemical behavior of the device is a necessary (but by no means sufficient) step toward the development of a functional device. In particular, effects to be eliminated are (i) electrochemically induced surface alteration through corrosion or reduction of the electrode surface and (ii) formation of hydrogen or oxygen bubbles inside the pore through water decomposition. Even though our motivation is to solve problems encountered in DNA transistor technology, in this paper we report on generic surface chemistry results. We investigated a variety of electrode-electrolyte-solvent systems with respect to their capability of suppressing water decomposition and maintaining surface integrity. We employed cyclic voltammetry and long-term amperometry as electrochemical test schemes, X-ray photoelectron spectroscopy, atomic force microscopy, and scanning, as well as transmission electron microscopy as analytical tools. Characterized electrode materials include thin films of Ru, Pt, nonstoichiometric TiN, and nonstoichiometric TiN carrying a custom-developed titanium oxide layer, as well as custom-oxidized nonstoichiometric TiN coated with a monolayer of hexadecylphosphonic acid (HDPA). We used distilled water as well as aqueous solutions of poly(ethylene glycol) (PEG-300) and glycerol as solvents. One millimolar KCl was employed as electrolyte in all solutions. Our results show that the HDPA-coated custom-developed titanium oxide layer effectively passivates the underlying TiN layer, eliminating any surface alterations through corrosion or reduction within a voltage window from -2 V to +2 V. Furthermore, we demonstrated that, by coating the custom-oxidized TiN samples with HDPA and increasing the concentration of PEG-300 or glycerol in aqueous 1 mM KCl solutions, water decomposition was suppressed within the same voltage window. Water dissociation was not detected when combining custom-oxidized HDPA-coated TiN electrodes with an aqueous 1 mM KCl-glycerol solution at a glycerol concentration of at least 90%. These results are applicable to any system that requires nanoelectrodes placed in aqueous solution at voltages that can activate electrochemical processes.

A simplified model of local structure in aqueous proline amino acid revealed by first-principles molecular dynamics simulations.

Aqueous proline solutions are deceptively simple as they can take on complex roles such as protein chaperones, cryoprotectants, and hydrotropic agents in biological processes. Here, a molecular level picture of proline/water mixtures is developed. Car-Parrinello ab initio molecular dynamics (CPAIMD) simulations of aqueous proline amino acid at the B-LYP level of theory, performed using IBM's Blue Gene/L supercomputer and massively parallel software, reveal hydrogen-bonding propensities that are at odds with the predictions of the CHARMM22 empirical force field but are in better agreement with results of recent neutron diffraction experiments. In general, the CPAIMD (B-LYP) simulations predict a simplified structural model of proline/water mixtures consisting of fewer distinct local motifs. Comparisons of simulation results to experiment are made by direct evaluation of the neutron static structure factor S(Q) from CPAIMD (B-LYP) trajectories as well as to the results of the empirical potential structure refinement reverse Monte Carlo procedure applied to the neutron data.

Tuneable poration: host defense peptides as sequence probes for antimicrobial mechanisms.

The spread of antimicrobial resistance stimulates discovery strategies that place emphasis on mechanisms circumventing the drawbacks of traditional antibiotics and on agents that hit multiple targets. Host defense peptides (HDPs) are promising candidates in this regard. Here we demonstrate that a given HDP sequence intrinsically encodes for tuneable mechanisms of membrane disruption. Using an archetypal HDP (cecropin B) we show that subtle structural alterations convert antimicrobial mechanisms from native carpet-like scenarios to poration and non-porating membrane exfoliation. Such distinct mechanisms, studied using low- and high-resolution spectroscopy, nanoscale imaging and molecular dynamics simulations, all maintain strong antimicrobial effects, albeit with diminished activity against pathogens resistant to HDPs. The strategy offers an effective search paradigm for the sequence probing of discrete antimicrobial mechanisms within a single HDP.

Author Correction: Tuneable poration: host defense peptides as sequence probes for antimicrobial mechanisms.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Engineering monolayer poration for rapid exfoliation of microbial membranes.

The spread of bacterial resistance to traditional antibiotics continues to stimulate the search for alternative antimicrobial strategies. All forms of life, from bacteria to humans, are postulated to rely on a fundamental host defense mechanism, which exploits the formation of open pores in microbial phospholipid bilayers. Here we predict that transmembrane poration is not necessary for antimicrobial activity and reveal a distinct poration mechanism that targets the outer leaflet of phospholipid bilayers. Using a combination of molecular-scale and real-time imaging, spectroscopy and spectrometry approaches, we introduce a structural motif with a universal insertion mode in reconstituted membranes and live bacteria. We demonstrate that this motif rapidly assembles into monolayer pits that coalesce during progressive membrane exfoliation, leading to bacterial cell death within minutes. The findings offer a new physical basis for designing effective antibiotics.

Structural correlations and motifs in liquid water at selected temperatures: ab initio and empirical model predictions.

To gain further insight into liquid water's structure and explore the role of different physical forces underlying the interaction between water molecules, the radial and angular structure of water is probed as a function of temperature for a carefully selected set of theoretical models. Simulations are performed with empirical rigid, empirical polarizable, empirical flexible with classical and quantum nuclei, and ab initio models with classical nuclei at 300 and 353 K and quantum nuclei at 300 K. The predicted radial distribution functions, spatial maps, and angular distributions of the neighboring water molecules are consistent with a model of liquid water in which water molecules are tetrahedrally coordinated. In addition, three-dimensional joint distribution functions are introduced and analyzed. By comparison of the functions obtained for hexagonal ice to those of liquid water, several thermally disordered, ice-like cluster structures are identified in the fluid.

Solution structure of the aqueous model peptide N-methylacetamide.

Classical molecular dynamics simulations of aqueous N-methylacetamide (NMA) have been performed across a concentration range at 308 K. This peptidic fragment molecule is a useful model for investigating water/peptide hydrogen bond competition. The simulations predict considerable NMA self-association even at low concentrations with a concentration-dependent increase in the ratio of branched to linear clusters. Water-mediated NMA contacts are a feature of this regime, manifested by an unexpected increase in the number of short NMA oxygen contacts arising from water bridge motifs. In contrast, bulk water structure is significantly disrupted by the addition of even small quantities of NMA. With increases in NMA concentration water molecules become progressively more isolated, forming dimers and trimers hydrogen-bonded to NMA. The mixture in this concentration regime may therefore offer a minimal model system for certain structural properties of interior water buried in protein cavities and hydrogen-bonded to mainchain peptide groups.

Ab initio and empirical model MD simulation studies of solvent effects on the properties of N-methylacetamide along a cis-trans isomerization pathway.

The properties of N-methylacetamide along a cis-trans isomerization pathway described by twisting about the C(O)-N bond are examined at finite temperature both in vacuo and in explicit water solvent. Two distinctly different theoretical descriptions, an ab initio (DFT-BLYP) and an empirical (CHARMM22) model, are studied in order to permit an assessment of the dominant forces active in the system. An analysis of the solvent structure at equilibrium and changes in solvation structure accompanying isomerization is, therefore, given for each model. Many-body polarization effects absent under CHARMM22 but present in the ab initio model are found to have a profound influence on the system. The electronic structure of the NMA molecule predicted by the ab initio method along the reaction coordinate is examined in order to shed further light on changes in peptide "partial-double" bond character [C(O)-N] as isomerization takes place. A new statistical-mechanical interpretation of the entropy change during a chemical reaction is presented to help interpret the thermochemistry of the simple reaction.

Crown Graphene Nanomeshes: Highly Stable Chelation-Doped Semiconducting Materials.

Graphene nanomeshes (GNMs) formed by the creation of pore superlattices in graphene are a possible route to graphene-based electronics due to their semiconducting properties, including the emergence of fractional electronvolt band gaps. The utility of GNMs would be markedly increased if a scheme to stably and controllably dope them was developed. In this work, a chemically motivated approach to GNM doping based on selective pore-perimeter passivation and subsequent ion chelation is proposed. It is shown by first-principles calculations that ion chelation leads to stable doping of the passivated GNMs-both n- and p-doping are achieved within a rigid-band picture. Such chelated or "crown" GNM structures are stable, high mobility semiconducting materials possessing intrinsic doping-concentration control; these can serve as building blocks for edge-free graphene nanoelectronics including GNM-based complementary metal oxide semiconductor (CMOS)-type logic switches.

High response piezoelectric and piezoresistive materials for fast, low voltage switching: simulation and theory of transduction physics at the nanometer-scale.

Field effect transistors are reaching the limits imposed by the scaling of materials and the electrostatic gating physics underlying the device. In this Communication, a new type of switch based on different physics, which combines known piezoelectric and piezoresistive materials, is described and is shown by theory and simulation to achieve gigahertz digital switching at low voltage (0.1 V).