Monovalent ion-mediated charge-charge interactions drive aggregation of surface-functionalized gold nanoparticles.

Monolayer-protected metal nanoparticles (NPs) are not only promising materials with a wide range of potential industrial and biological applications, but they are also a powerful tool to investigate the behaviour of matter at nanoscopic scales, including the stability of dispersions and colloidal systems. This stability is dependent on a delicate balance between attractive and repulsive interactions that occur in the solution, and it is described in quantitative terms by the classic Derjaguin-Landau-Vewey-Overbeek (DLVO) theory, that posits that aggregation between NPs is driven by van der Waals interactions and opposed by electrostatic interactions. To investigate the limits of this theory at the nanoscale, where the continuum assumptions required by the DLVO theory break down, here we investigate NP dimerization by computing the Potential of Mean Force (PMF) of this process using fully atomistic MD simulations. Serendipitously, we find that electrostatic interactions can lead to the formation of metastable NP dimers at physiological ion concentrations. These dimers are stabilized by complexes formed by negatively charged ligands belonging to distinct NPs that are bridged by positively charged monovalent ions present in solution. We validate our findings by collecting tomographic EM images of NPs in solution and by quantifying their radial distribution function, that shows a marked peak at interparticle distance comparable with that of MD simulations. Taken together, our results suggest that not only van der Waals interactions, but also electrostatic interactions mediated by monovalent ions at physiological concentrations, contribute to attraction between nano-sized charged objects at very short length scales.

Multi-sulfonated ligands on gold nanoparticles as virucidal antiviral for Dengue virus.

Dengue virus (DENV) causes 390 million infections per year. Infections can be asymptomatic or range from mild fever to severe haemorrhagic fever and shock syndrome. Currently, no effective antivirals or safe universal vaccine is available. In the present work we tested different gold nanoparticles (AuNP) coated with ligands ω-terminated with sugars bearing multiple sulfonate groups. We aimed to identify compounds with antiviral properties due to irreversible (virucidal) rather than reversible (virustatic) inhibition. The ligands varied in length, in number of sulfonated groups as well as their spatial orientation induced by the sugar head groups. We identified two candidates, a glucose- and a lactose-based ligand showing a low EC50 (effective concentration that inhibit 50% of the viral activity) for DENV-2 inhibition, moderate toxicity and a virucidal effect in hepatocytes with titre reduction of Median Tissue Culture Infectious Dose log10TCID50 2.5 and 3.1. Molecular docking simulations complemented the experimental findings suggesting a molecular rationale behind the binding between sulfonated head groups and DENV-2 envelope protein.

Reproducibility warning: The curious case of polyethylene glycol 6000 and spheroid cell culture.

Reproducibility of results is essential for a well-designed and conducted experiment. Several reasons may originate failure in reproducing data, such as selective reporting, low statistical power, or poor analysis. In this study, we used PEG6000 samples from different distributors and tested their capability inducing spheroid formation upon surface coating. MALDI-MS, NMR, FTIR, and Triple SEC analysis of the different PEG60000s showed nearly identical physicochemical properties different, with only minor differences in mass and hydrodynamic radius, and AFM analysis showed no significant differences in the surface coatings obtained with the available PEG6000s. Despite these similarities, just one showed a highly reproducible formation of spheroids with different cell lines, such as HT-29, HeLa, Caco2, and PANC-1. Using the peculiar PEG6000 sample and a reference PEG6000 chosen amongst the others as control, we tested the effect of the cell/PEG interaction by incubating cells in the PEG solution prior to cell plating. These experiments indicate that the spheroid formation is due to direct interaction of the polymer with the cells rather than by interaction of cells with the coated surfaces. The experiments point out that for biological entities, such as cells or tissues, even very small differences in impurities or minimal variations in the starting product can have a very strong impact on the reproducibility of data.

Determination and evaluation of the nonadditivity in wetting of molecularly heterogeneous surfaces.

The interface between water and folded proteins is very complex. Proteins have "patchy" solvent-accessible areas composed of domains of varying hydrophobicity. The textbook understanding is that these domains contribute additively to interfacial properties (Cassie's equation, CE). An ever-growing number of modeling papers question the validity of CE at molecular length scales, but there is no conclusive experiment to support this and no proposed new theoretical framework. Here, we study the wetting of model compounds with patchy surfaces differing solely in patchiness but not in composition. Were CE to be correct, these materials would have had the same solid-liquid work of adhesion (WSL ) and time-averaged structure of interfacial water. We find considerable differences in WSL , and sum-frequency generation measurements of the interfacial water structure show distinctively different spectral features. Molecular-dynamics simulations of water on patchy surfaces capture the observed behaviors and point toward significant nonadditivity in water density and average orientation. They show that a description of the molecular arrangement on the surface is needed to predict its wetting properties. We propose a predictive model that considers, for every molecule, the contributions of its first-nearest neighbors as a descriptor to determine the wetting properties of the surface. The model is validated by measurements of WSL in multiple solvents, where large differences are observed for solvents whose effective diameter is smaller than ∼6 Å. The experiments and theoretical model proposed here provide a starting point to develop a comprehensive understanding of complex biological interfaces as well as for the engineering of synthetic ones.

Stable Ultraconcentrated and Ultradilute Colloids of CsPbX3 (X = Cl, Br) Nanocrystals Using Natural Lecithin as a Capping Ligand.

Attaining thermodynamic stability of colloids in a broad range of concentrations has long been a major thrust in the field of colloidal ligand-capped semiconductor nanocrystals (NCs). This challenge is particularly pressing for the novel NCs of cesium lead halide perovskites (CsPbX3; X = Cl, Br) owing to their highly dynamic and labile surfaces. Herein, we demonstrate that soy lecithin, a mass-produced natural phospholipid, serves as a tightly binding surface-capping ligand suited for a high-reaction yield synthesis of CsPbX3 NCs (6-10 nm) and allowing for long-term retention of the colloidal and structural integrity of CsPbX3 NCs in a broad range of concentrations-from a few ng/mL to >400 mg/mL (inorganic core mass). The high colloidal stability achieved with this long-chain zwitterionic ligand can be rationalized with the Alexander-De Gennes model that considers the increased particle-particle repulsion due to branched chains and ligand polydispersity. The versatility and immense practical utility of such colloids is showcased by the single NC spectroscopy on ultradilute samples and, conversely, by obtaining micrometer-thick, optically homogeneous dense NC films in a single spin-coating step from ultraconcentrated colloids.

Quantitative 3D determination of self-assembled structures on nanoparticles using small angle neutron scattering.

The ligand shell (LS) determines a number of nanoparticles' properties. Nanoparticles' cores can be accurately characterized; yet the structure of the LS, when composed of mixture of molecules, can be described only qualitatively (e.g., patchy, Janus, and random). Here we show that quantitative description of the LS' morphology of monodisperse nanoparticles can be obtained using small-angle neutron scattering (SANS), measured at multiple contrasts, achieved by either ligand or solvent deuteration. Three-dimensional models of the nanoparticles' core and LS are generated using an ab initio reconstruction method. Characteristic length scales extracted from the models are compared with simulations. We also characterize the evolution of the LS upon thermal annealing, and investigate the LS morphology of mixed-ligand copper and silver nanoparticles as well as gold nanoparticles coated with ternary mixtures. Our results suggest that SANS combined with multiphase modeling is a versatile approach for the characterization of nanoparticles' LS.

Plasmon-resonant nanoparticles and nanostars with magnetic cores: synthesis and magnetomotive imaging.

Plasmon-resonant gold nanostars (NSTs) with magnetic cores were synthesized by a multistep sequence from superparamagnetic Fe3O4 nanoparticles (NPs) and evaluated as optical contrast agents under magnetomotive (MM) imaging conditions. Core-shell Fe3O4@Au NPs were prepared in nonpolar organic solvents with nanometer control over shell thickness and with good epitaxy to the Fe3O4 surface. Anisotropic growth was performed in micellar solutions of cetyltrimethylammonium bromide (CTAB) under mildly reducing conditions, resulting in NSTs with physical features similar to those produced from colloidal gold seeds. NSTs could be produced below 100 nm from tip to tip, but seed size had a significant impact on growth habit, with larger seed particles producing submicrometer-sized "morning stars". Both NSTs and aggregated core-shell NPs are responsive to in-plane magnetic field gradients and can provide enhanced near-infrared (NIR) contrast under MM conditions, but do so by different mechanisms. NSTs can modulate polarized NIR scattering with minimal translational motion, giving the appearance of a periodic but stationary "blinking", whereas core-shell NP aggregates require lateral displacement for signal modulation. The polarization-sensitive MM imaging modality offers the dual advantage of enhanced signal quality and reduced background signal and can be applied toward the detection of magnetomotive NSTs in heterogeneous biological samples, as illustrated by their detection inside of granular cells such as macrophages.

Gyromagnetic imaging: dynamic optical contrast using gold nanostars with magnetic cores.

Plasmon-resonant nanoparticles with optical scattering in the near-infrared (NIR) are valuable contrast agents for biophotonic imaging and may be detected at the single-particle limit against a dark background, but their contrast is often limited in environments with high noise. Here we consider gyromagnetic imaging as a dynamic mode of optical contrast, using gold nanostars with superparamagnetic cores. The nanostars exhibit polarization-sensitive NIR scattering and can produce a frequency-modulated signal in response to a rotating magnetic field gradient. This periodic "twinkling" can be converted into Fourier-domain images with a dramatic reduction in background. We demonstrate gyromagnetic imaging of nanostars inside of tumor cells, using broadband excitation: while their time-domain signals are obscured by incoherent scattering, their Fourier-domain signals can be clearly resolved in less than a second. The gyromagnetically active nanostars do not cause a loss in viability, and can even have a mild stimulatory effect on cell growth.

Attachment of nanoparticles to the AFM tips for direct measurements of interaction between a single nanoparticle and surfaces.

Here we report a universal method of attachment/functionalization of tips for atomic force microscope (AFM) with nanoparticles. The particles of interest are glued to the AFM tip with epoxy. While the gluing of micron size particles with epoxy has been known, attachment of nanoparticles was a problem. The suggested method can be used for attachment of virtually any solid nanoparticles. Approximately every other tip prepared with this method has a single nanoparticle terminated apex. We demonstrate the force measurements between a single approximately 50 nm ceria nanoparticle and flat silica surface in aqueous media of different acidity (pH 4-9). Comparing forces measured with larger ceria particles ( approximately 500 nm), we show that the interaction with nanoparticles is qualitatively different from the interaction with larger particles.

AFM study of forces between silica, silicon nitride and polyurethane pads.

Interaction of silica and silicon nitride with polyurethane surfaces is rather poorly studied despite being of great interest for modern semiconductor industry, e.g., for chemical-mechanical planarization (CMP) processes. Here we show the results from the application of the atomic force microscopy (AFM) technique to study the forces between silica or silicon nitride (AFM tips) and polyurethane surfaces in aqueous solutions of different acidity. The polyurethane surface potentials are derived from the measured AFM data. The obtained potentials are in rather good agreement with measurements of zeta-potentials using the streaming-potentials method. Another important parameter, adhesion, is also measured. While the surface potentials of silica are well known, there are ambiguous results on the potentials of silicon nitride that is naturally oxidized. Deriving the surface potential of the naturally oxidized silicon nitride from our measurements, we show that it is not oxidized to silica despite some earlier published expectations.