Model-free description of polymer-coated gold nanoparticle dynamics in aqueous solutions obtained by Bayesian analysis of neutron spin echo data.

We present a neutron spin echo study of the nanosecond dynamics of polyethylene glycol (PEG) functionalized nanosized gold particles dissolved in D_{2}O at two temperatures and two different PEG molecular weights (400D and 2000D). The analysis of the neutron spin echo data was performed by applying a Bayesian approach to the description of time correlation function decays in terms of exponential terms, recently proved to be theoretically rigorous. This approach, which addresses in a direct way the fundamental issue of model choice in any dynamical analysis, provides here a guide to the most statistically supported way to follow the decay of the intermediate scattering functions I(Q,t) by basing on statistical grounds the choice of the number of terms required for the description of the nanosecond dynamics of the studied systems. Then, the presented analysis avoids from the start resorting to a preselected framework and can be considered as model free. By comparing the results of PEG-coated nanoparticles with those obtained in PEG2000 solutions, we were able to disentangle the translational diffusion of the nanoparticles from the internal dynamics of the polymer grafted to them, and to show that the polymer corona relaxation follows a pure exponential decay in agreement with the behavior predicted by coarse grained molecular dynamics simulations and theoretical models. This methodology has one further advantage: in the presence of a complex dynamical scenario, I(Q,t) is often described in terms of the Kohlrausch-Williams-Watts function that can implicitly represent a distribution of relaxation times. By choosing to describe the I(Q,t) as a sum of exponential functions and with the support of the Bayesian approach, we can explicitly determine when a finer-structure analysis of the dynamical complexity of the system exists according to the available data without the risk of overparametrization. The approach presented here is an effective tool that can be used in general to provide an unbiased interpretation of neutron spin echo data or whenever spectroscopy techniques yield time relaxation data curves.

Microcontact Printing Patterning of an HOPG Surface by an Inverse Electron Demand Diels-Alder Reaction.

The chemical modification of an sp2 hybridized carbon surface in a controllable manner is very challenging but also crucial for many applications. An inverse electron demand Diels-Alder (IEDDA) reaction using microcontact printing technique is introduced to spatially control the modification of a highly ordered pyrolytic graphite (HOPG) surface under ambient conditions. The covalent modification was characterized by Raman spectroscopy, XPS, and SECM. Tetrazine derivatives can effectively react with an HOPG surface and with microcontact printing methods resulting in spatially patterned surfaces being produced with micrometer-scale resolution.

Selective in situ potential-assisted SAM formation on multi electrode arrays.

The selective modification of individual components in a biosensor array is challenging. To address this challenge, we present a generalizable approach to selectively modify and characterize individual gold surfaces in an array, in an in situ manner. This is achieved by taking advantage of the potential dependent adsorption/desorption of surface-modified organic molecules. Control of the applied potential of the individual sensors in an array where each acts as a working electrode provides differential derivatization of the sensor surfaces. To demonstrate this concept, two different self-assembled monolayer (SAM)-forming electrochemically addressable ω-ferrocenyl alkanethiols (C11) are chemisorbed onto independent but spatially adjacent gold electrodes. The ferrocene alkanethiol does not chemisorb onto the surface when the applied potential is cathodic relative to the adsorption potential and the electrode remains underivatized. However, applying potentials that are modestly positive relative to the adsorption potential leads to extensive coverage within 10 min. The resulting SAM remains in a stable state while held at potentials <200 mV above the adsorption potential. In this state, the chemisorbed SAM does not significantly desorb nor do new ferrocenylalkythiols adsorb. Using three set applied potentials provides for controlled submonolayer alkylthiol marker coverage of each independent gold electrode. These three applied potentials are dependent upon the specifics of the respective adsorbate. Characterization of the ferrocene-modified electrodes via cyclic voltammetry demonstrates that each specific ferrocene marker is exclusively adsorbed to the desired target electrode.

Hydrogen bonding vs. molecule-surface interactions in 2D self-assembly of [C60]fullerenecarboxylic acids.

The adsorption of C60-malonic derivatives C61(CO2H)2 and C66(CO2H)12 on Au(111) and a pentafluorobenzenethiol-modified Au substrate (PFBT@Au) has been investigated using scanning tunneling microscopy (STM) at a liquid-solid interface. Monofunctionalized C61(CO2H)2 forms a hexagonal close-packed overlayer on Au(111) and individual aligned dimers on PFBT@Au(111). The difference is attributed to the nature of the substrateC61(CO2H)2 interaction (isotropic π-Au bonding vs. anisotropic PFBTCOOH interactions). Surprisingly, in both cases, the directionality of the COOHCOOH motif is compromised in favor of synergistic van der Waals/H bonding interactions. Such van der Waals contacts are geometrically unfeasible in hexafunctionalized C66(CO2H)12 and its assembly on Au(111) leads to a 2D molecular network controlled exclusively by H bonding. For both molecules, the "free" CO2H groups on the monolayer surface can engage in out-of-plane H bonding interaction resulting in the epitaxial growth of subsequent molecular layers.

Lipid Microdomains in Synapse Formation.

Membrane lipid rafts (i.e., cholesterol/sphingolipids domains) exhibit functional roles in both healthy and pathological states of the nervous system. However, due to their highly dynamic nature, it remains a challenge to characterize the fundamental aspects of lipid rafts that are important for specific neuronal processes. An experimental approach is presented here that allows for the interfacing of living neurons with an experimentally accessible model membrane where lipid order in cellular rafts can be reproducibly mimicked. It is demonstrated that coexisting lipid microdomains in model membranes can regulate axonal guidance and establish stable presynaptic contacts when interfaced with neurons in vitro. Experimental evidence is provided where specific functional groups and lateral organizations are favored by neurons in establishing synaptic connections. The model membrane platform presented in this work provides an accessible and direct means to investigate how lipid rafts regulate synapse formation. This experimental platform can similarly be extended to explore a variety of other cellular events where lipid lateral organization is believed to be important.

Synthesis of 3-chloro-6-((4-(di-tert-butyl[(18)F]fluorosilyl)-benzyl)oxy)-1,2,4,5-tetrazine ([(18)F]SiFA-OTz) for rapid tetrazine-based (18)F-radiolabeling.

An efficient method to prepare the (18)F-labeled tetrazine-derivative [(18)F]-SiFA-OTz for bioorthogonal radiochemistry was developed. [(18)F]-SiFA-OTz can be synthesized with a radiochemical yield of 78 ± 5% within 25 min and can quantitatively react with a model strained dienophile, trans-cyclooctenol.

Characterization of a gold coated cantilever surface for biosensing applications.

Cantilever based sensors are a promising tool for a very diverse spectrum of biological sensors. They have been used for the detection of proteins, DNA, antigens, bacteria viruses and many other biologically relevant targets. Although cantilever sensing has been described for over 20 years, there are still no viable commercial cantilever-based sensing products on the market. Several reasons can be found for this - a lack of detailed understanding of the origin of signals being an important one. As a consequence application-relevant issues such as shelf life and robust protocols distinguishing targets from false responses have received very little attention. Here, we will discuss a cantilever sensing platform combined with an electrochemical system. The detected surface stress signal is modulated by applying a square wave potential to a gold coated cantilever. The square wave potential induces adsorption and desorption onto the gold electrode surface as well as possible structural changes of the target and probe molecules on the cantilever surface resulting in a measurable surface stress change. What sets this approach apart from regular cantilever sensing is that the quantification and identification of observed signals due to target-probe interactions are not only a function of stress value (i.e. amplitude), but also of the temporal evolution of the stress response as a function of the rate and magnitude of the applied potential change, and the limits of the potential change. This paper will discuss three issues that play an important role in future successful applications of cantilever-based sensing. First, we will discuss what is required to achieve a large surface stress signal to improve sensitivity. Second, a mechanism to achieve an optimal probe density is described that improves the signal-to-noise ratio and response times of the sensor. Lastly, lifetime and long term measurements are discussed.

Interfacing living cells and spherically supported bilayer lipid membranes.

Spherically supported bilayer lipid membranes (SS-BLMs) exhibiting co-existing membrane microdomains were created on spherical silica substrates. These 5 µm SiO2-core SS-BLMs are shown to interact dynamically when interfaced with living cells in culture, while keeping the membrane structure and lipid domains on the SS-BLM surface intact. Interactions between the SS-BLMs and cellular components are examined via correlating fluorescently labeled co-existing microdomains on the SS-BLMs, their chemical composition and biophysical properties with the consequent organization of cell membrane lipids, proteins, and other cellular components. This approach is demonstrated in a proof-of-concept experiment involving the dynamic organization of cellular cytoskeleton, monitored as a function of the lipid domains of the SS-BLMs. The compositional versatility of SS-BLMs provides a means to address the relationship between the phenomenon of lipid phase separation and the other contributors to cell membrane lateral heterogeneity.

Tridentate benzylthiols on Au(111): control of self-assembly geometry.

A set of hexasubstituted benzene derivatives with three thiol groups in the 1, 3, 5 positions and varied aliphatic substituents in the 2, 4, 6 positions (Me3-BTMT, Et3-BTMT, ODe3-BTMT) has been synthesized and self-assembled on Au(111). The resulting self-assembled monolayers (SAMs) are characterized by scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and electrochemistry. The molecular orientation and long-range order are affected by the "gear effect" of the hexasubstituted benzene ring and van der Waals interactions between the physisorbed alkyl chains drive. Me3-BTMT adopts a standing up orientation which results in the highest molecular surface density but also the lowest degree of chemisorption (1 to 2 Au­S bonds per molecule). In contrast, Et3-BTMT favors a lying down orientation with a greater number of surface-bonded thiol groups (2 to 3) per molecule, associated with the peculiar geometry of this molecule. Finally, ODe3-BTMT adsorbs mainly in a lying down orientation, forming the SAM with the highest degree of chemisorption (all thiol groups are gold-bonded) and the lowest molecular areal density.

High thermal stability of block copolymer-capped Au and Cu nanoparticles.

Producing solution-based metal nanoparticles that do not agglomerate at elevated temperatures remains challenging. We show that thermally stable Au and Cu nanoparticles can be prepared using polystyrene-poly(4-vinylpyridine) diblock copolymers as capping agents. These materials remain stable when their solutions are subjected to prolonged heating up to 160 °C for more than 48 h. These conditions are sufficient for applications in most wet chemical processes and reactions.

Rapid (18)F-labeling and loading of PEGylated gold nanoparticles for in vivo applications.

Water-soluble 3 nm maleimide-terminated PEGylated gold nanoparticles (maleimide-AuNP) were synthesized in both partially hydrolyzed and nonhydrolyzed forms. Both of these maleimide-AuNPs, when reacted with the silicon-fluorine prosthetic group [(18)F]SiFA-SH, resulted in radiolabeled AuNPs. These NPs were readily purified with high radiochemical yields (RCY) of 60-80% via size exclusion chromatography. Preliminary small animal positron emission tomography (PET) measurements in healthy rats gives information about the pathway of excretion and the stability of the radioactive label in vivo. The partially hydrolyzed [(18)F]SiFA-maleimide-AuNPs shows uptake in the brain region of interest (ROI) (> 0.13%ID/g) which was confirmed by ex vivo examination of the thoroughly perfused rat brain. The multiple maleimide end groups on the AuNP surface also allows for the simultaneous incorporation of [(18)F]SiFA-SH and a bioactive peptide (cysteine-modified octreotate, cys-TATE, which can bind to somatostatin receptor subtypes 2 and 5) in a proof-of-concept study. The well-defined Michael addition reaction between various thiol containing molecules and the multifunctionalized maleimide-AuNPs thus offers an opportunity to develop a new bioconjugation platform for new diagnostics as well as therapeutics.

Directing the assembly of gold nanoparticles with two-dimensional molecular networks.

Lamellar patterns resulting from the adsorption of p-dialkoxybenzene derivatives on HOPG have been investigated as molecular templates for directing the assembly of thiol-capped gold nanoparticles (AuNP). STM characterization at the liquid-solid interface reveals the periodic arrangement of AuNP on top of the self-assembled molecular network (SAMN), spanning hundreds of nanometers. The resulting superlattices are notably different from the close-packed structures formed by spherical nanoparticles during evaporative drying. The templating effect is based on van der Waals interactions of the alkyl chains of the SAMN and AuNP, and the assembly efficiency is greatest when these chains are of similar length.

Chemical modification of single walled carbon nanotubes with tetrazine-tethered gold nanoparticles via a Diels-Alder reaction.

A versatile methodology for the modification of single walled carbon nanotubes (SWCNTs) through an inverse electron demand Diels-Alder reaction with tetrazine-AuNPs (-AuNPs) under ambient conditions is described. A robust covalently bonded hybrid nanocomposite is formed.

An electrochemically controlled microcantilever biosensor.

An oligonucleotide-based electrochemically controlled gold-coated microcantilever biosensor that can transduce specific biomolecular interactions is reported. The derivatized microcantilever exhibits characteristic surface stress time course patterns in response to an externally applied periodic square wave potential. Experiments demonstrate that control of the surface charge density with an electrode potential is essential to producing a sensor that exhibits large, reproducible surface stress changes. The time course of surface stress changes are proposed to be linked to an electrochemically mediated competition between the adsorption of solution-based ions and the single- or double-stranded oligonucleotides tethered to the gold surface. A similar potential-actuated change in surface stress also results from the interaction between an oligonucleotide aptamer and its cognate ligand, demonstrating the broad applicability of this methodology.

A molecular and thermodynamic view of the assembly of gold nanoparticles in nematic liquid crystal.

The molecular interactions driving the assembly of gold nanoparticles (AuNPs) in a nematic liquid crystal (LC) are directly detected by nuclear magnetic resonance (NMR) spectroscopy and thermodynamically analyzed. The orientational orders of the selectively deuterated LC matrix and AuNP ligands, each separately followed by variable temperature (2)H NMR as a function of particle concentration, were observed to be strongly correlated. The mechanism of the reversible formation of long-range, quasi-periodic nanoparticle structures is attributed to the coupling of the AuNP ligands to the LC matrix, inducing an isotropic-nematic biphasic state. Experimentally validated thermodynamic modeling shows that, in contrast to colloidal nematics that are dominated by elastic forces, nematic dispersions of nanoparticles self-organize through a subtle balance of entropic forces and excluded volume, interface-mediated mesogen and nanoparticle molecular interactions, and couplings between conserved and nonconserved order parameters. Fine-tuning of these interactions through ligand and mesogen chemistry, together with mesoscale modeling, provides a route for materials innovations by merging structured fluid physics and nanoscience.

Entanglement-controlled subdiffusion of nanoparticles within concentrated polymer solutions.

We describe x-ray photon correlation spectroscopy (XPCS) experiments tracking the motion of gold nanoparticles within solutions of high-molecular-weight polystyrene. Over displacements from nanometers to tens of nanometers, the particles undergo subdiffusive motion that is dictated by the temporal evolution of the entangled polymer mesh in the immediate vicinity of the particles. The results thus provide a novel microscopic dynamical characterization of this key structural property of polymers and more broadly demonstrate the capability of XPCS-based microrheology to interrogate heterogeneous mechanical environments in nanostructured soft materials.

Preparation of water-soluble maleimide-functionalized 3 nm gold nanoparticles: a new bioconjugation template.

We present an efficient methodology to prepare maleimide-tethered, water-soluble gold nanoparticles (maleimide-AuNPs). The maleimide-AuNPs were prepared in the protected form and are readily recovered via a retro-Diels-Alder reaction. The maleimide-AuNPs were fully characterized by (1)H NMR, TGA, TEM, and XPS and were determined to have a gold core with an average size of 3.2 ± 0.8 nm; each core contains about 1000 gold atoms and is surrounded by 30 maleimide-terminated ligands and 60 thiolated PEG ligands. The maleimide-AuNPs efficiently react with rhodamine 123 and cysteine and are a promising template for biological applications.

Facile phase transfer of large, water-soluble metal nanoparticles to nonpolar solvents.

The facile phase-transfer of large, water-soluble metal nanoparticles to nonpolar solvent is reported here. Thiol-terminated polystyrene (PS-SH) is ligand-exchanged onto water-soluble metal nanoparticles in single-phase acetone/water mixtures, generating a precipitate. The solvent is then removed and the particles are redissolved in nonpolar solvent. This approach is demonstrated for nanoparticles of different metal (Au and Ag), size (3 to >100 nm), shape (spheres, rods, and wires, etc.), and leaving ligand (citrate, cetyltrimethylammonium bromide, poly(vinylpyrrolidone), and 4-dimethylaminopyridine. The resulting PS-SH-stabilized nanoparticles maintain their initial size and shape, and are highly stable. They are soluble in various organic solvents (toluene, benzene, chloroform, dichloromethane, and tetrahydrofuran), and can be readily dried, purified, and re-dissolved. This method makes possible the utilization of a full range of existing nanoparticle cores in nonpolar solvents with a single ligand. It provides access to numerous nanomaterials that cannot be obtained through direct synthesis in nonpolar solvent, and is expected to be of significant value in a number of applications.

Electrochemical synthesis of Ag(0)/A2S heterojunctions templated on pre-formed Ag2S nanowires.

Hybrid metal/ionic conductor nanostructures are of considerable interest due to their potential use as resistive switches, and are envisioned as the next generation of memory devices. We present here the electrochemical conversion of ionic and semi-conducting Ag(2)S nanowires (NW) into a range of hybrid nanostructures. Partial electrochemical reduction of Au/Ag(2)S NW/Au junctions allows one to form Ag(0) NW/Ag(2)S NW and Ag(0) NW/Ag(2)S NW/Ag(0) NW heterojunctions. Control over the quantity of Ag(0) NW within the junctions is presented along with its influence on the conductivity of the junctions. We demonstrate the use of this technique to make functional Au/Ag(0) NW/Ag(2)S NW/Au resistive switches.

Switching atomic friction by electrochemical oxidation.

Friction between the sliding tip of an atomic force microscope and a gold surface changes dramatically upon electrochemical oxidation of the gold surface. Atomic-scale variations of the lateral force reveal details of the friction mechanisms. Stick-slip motion with atomic periodicity on perfect Au(111) terraces exhibits extremely low friction and almost no dependence on load. Significant friction is observed only above a load threshold at which wear of the surface is initiated. In contrast, irregular stick-slip motion and a linear increase of friction with load are observed on electrochemically oxidized surfaces. The observations are discussed with reference to the amorphous structure of the oxo-hydroxide surface and atomic place exchange mechanisms upon oxidation. Reversible, fast switching between the two states of friction has been achieved in both perchloric and sulfuric acid solutions.