Non-covalent Surface Research Articles

Exploring the Possibility of Noncovalently Surface Bound Molecular Quantum-Dot Cellular Automata: Theoretical Simulations of Deposition of Double-Cage Fluorinated Fullerenes on Ag(100) Surface

The double-cage fluorinated fullerene (C20F18(NH)2C20F18) has been suggested to be a new kind of molecular quantum-dot cellular automata (MQCA) candidate. The possibility of noncovalently binding these candidate molecules on silver substrates is explored by molecular dynamics (MD) simulations. It is demonstrated that the candidate molecules can deposit on Ag(100) surface and form ordered MQCA arrays in both head-to-tail and side-by-side styles. The side-by-side array can keep intact even at room temperature, while the head-to-tail array shows larger thermal fluctuations. In comparison with the Ag(100) surface, ordered arrays can only be observed in the side-by-side style at low temperatures on Ag(111) surface. Density functional theory (DFT) calculations of the charge redistribution of the candidate, in response to an electrostatic driver, show that the QCA function of the candidate still maintains with the introduction of the Ag surface. In addition, a simple (Coulomb) electrostatic model is proposed to simulate the dynamical signal transmission in our MQCA wire. The transmission time is affected by the wire length as well as the long-range intercellular electrostatic interactions.

Tailor-Made Fibrous Nanohydroxyapatite/Polydimethylsiloxane Composites: Excavating the Role of Nanofiller Aspect Ratio, Amorphicity, and Noncovalent Surface Interaction

This work holds significance in designing biomimetic implants where biocompatibility and strength are two critical concerns. In the work mentioned herein, hydroxyapatite nanofibers of varying aspect ratios have been synthesized by the soft template assisted method. These nanoparticulates have been successfully introduced into the polydimethylsiloxane (PDMS) matrix through a solution casting technique, and this is probably the first successful attempt made. Nanocomposites prepared with longer nanofibers (300–500 nm length) showed more improvement in various physicomechanical and thermal properties compared with those prepared with lower aspect ratio nanofibers (10.3 versus 4.5). In-depth analysis revealed that a combined effect of several factors leads to these differences. Besides the most important factor, viz., aspect ratio of the nanofibers, the amorphicity of nanofibers and adherence of polymer on the nanofiller surface, i.e., noncovalent surface modification of nanofiller and restriction of microcrys...

Surface modification of stereoregular and stereocomplex poly(methyl methacrylate) films with biologically identified peptides

Biologically identified peptides that bind to the surfaces of isotactic poly(methyl methacrylate) (PMMA), syndiotactic PMMA, and their assembled stereocomplex films were used as noncovalent surface modifiers. Each peptide was biotinylated and immobilized onto the PMMA films to function as a linker for the subsequent immobilization of streptavidin. We demonstrated that the PMMA species had a great impact on the peptides' abilities to functionally modify the film surfaces.

Toxicity of aqueous C70‐gallic acid suspension in Daphnia magna

The present study assessed the toxic effects of stable aqueous colloidal suspensions of gallic-acid-stabilized C(70) fullerene on Daphnia magna. The suspensions were stabilized through noncovalent surface modification with gallic acid. In addition to whole-organism responses, changes in antioxidative processes in D. magna were quantified. Acute toxicity was observed with 96LC50 for C(70) -gallic acid of 0.4 ± 0.1 mg/L C(70) . Daphnia magna fecundity was significantly reduced in 21-d bioassays at C(70) -gallic aqcid concentrations below quantifiable limits. Antioxidant enzyme activities of glutathione peroxidase and superoxide dismutase as well as lipid peroxidation suggested that exposed organisms experienced oxidative stress. Microscopic techniques used to determine cellular toxicity via apoptosis proved unsuccessful.

Liposomes: From a Clinically Established Drug Delivery System to a Nanoparticle Platform for Theranostic Nanomedicine

For decades, clinicians have used liposomes, self-assembled lipid vesicles, as nanoscale systems to deliver encapsulated anthracycline molecules for cancer treatment. The more recent proposition to combine liposomes with nanoparticles remains at the preclinical development stages; however, such hybrid constructs present great opportunities to engineer theranostic nanoscale delivery systems, which can combine simultaneous therapeutic and imaging functions. Many novel nanoparticles of varying chemical compositions are being developed in nanotechnology laboratories, but further chemical modification is often required to make these structures compatible with the biological milieu in vitro and in vivo. Such nanoparticles have shown promise as diagnostic and therapeutic tools and generally offer a large surface area that allows covalent and non-covalent surface functionalization with hydrophilic polymers, therapeutic moieties, and targeting ligands. In most cases, such surface manipulation diminishes the theranostic properties of nanoparticles and makes them less stable. From our perspective, liposomes offer structural features that can make nanoparticles biocompatible and present a clinically proven, versatile platform for further enhancement of the pharmacological and diagnostic efficacy of nanoparticles. In this Account, we describe two examples of liposome-nanoparticle hybrids developed as theranostics: liposome-quantum dot hybrids loaded with a cytotoxic drug (doxorubicin) and artificially enveloped adenoviruses. We incorporated quantum dots into lipid bilayers, which rendered them dispersible in physiological conditions. This overall vesicular structure allowed them to be loaded with doxorubicin molecules. These structures exhibited cytotoxic activity and labeled cells both in vitro and in vivo. In an alternative design, lipid bilayers assembled around non-enveloped viral nanoparticles and altered their infection tropism in vitro and in vivo with no chemical or genetic capsid modifications. Overall, we have attempted to illustrate how alternative strategies to incorporate nanoparticles into liposomal nanostructures can overcome some of the shortcomings of nanoparticles. Such hybrid structures could offer diagnostic and therapeutic combinations suitable for biomedical and even clinical applications.

Silica nanoparticles with a substrate switchable luminescence

Silica nanoparticles with visible (Tb and Ru doped), near IR (Yb doped) and dual visible-near IR luminescence (Ru-Yb doped) were obtained by reverse w/o microemulsion procedure. Plenty of luminescent complexes (from 4900 to 10000) encapsulated into each nanoparticle ensures the intensive luminescence of nanoparticles and their applicability as biomarkers. The silica surface decoration by definite anchor groups is the required step for the gaining to these nanoparticles marking and sensing functions. Thus covalent and non-covalent surface modification of these nanoparticles was developed to provide the binding with biotargets and sensing of anions. The dicationic surfactant coating of negatively charged Tb(III)-TCAS doped silica nanoparticles was chosen as the basis for the anion responsible system. The reversible insertion of the quenching anions (namely phenol red) into the surfactant based layer at the surface of luminescent nanoparticles switches off the Tb-centered luminescence. In turn the reversible reestablishment of the luminescence results from the competitive insertion of the non-quenching anions into the surfactant layer at the silica/water interface. The hydrophobic anions exemplified by dodecylsulfates versus hydrophilic ones (hydrophosphates) are preferable in the competition with phenol red anions.

The E2-25K ubiquitin-associated (UBA) domain aids in polyubiquitin chain synthesis and linkage specificity

E2-25K is an ubiquitin-conjugating enzyme with the ability to synthesize Lys48-linked polyubiquitin chains. E2-25K and its homologs represent the only known E2 enzymes which contain a C-terminal ubiquitin-associated (UBA) domain as well as the conserved catalytic ubiquitin-conjugating (UBC) domain. As an additional non-covalent binding surface for ubiquitin, the UBA domain must provide some functional specialization. We mapped the protein–protein interface involved in the E2-25K UBA/ubiquitin complex by solution nuclear magnetic resonance (NMR) spectroscopy and subsequently modeled the structure of the complex. Domain–domain interactions between the E2-25K catalytic UBC domain and the UBA domain do not induce significant structural changes in the UBA domain or alter the affinity of the UBA domain for ubiquitin. We determined that one of the roles of the C-terminal UBA domain, in the context of E2-25K, is to increase processivity in Lys48-linked polyubiquitin chain synthesis, possibly through increased binding to the ubiquitinated substrate. Additionally, we see evidence that the UBA domain directs specificity in polyubiquitin chain linkage.

Decorating carbon nanotubes with polyethylene glycol-coated magnetic nanoparticles for implementing highly sensitive enzyme biosensors

Superparamagnetic Fe3O4 nanoparticles were coated with (3-aminopropyl)triethoxysilane and further branched with monomethoxypolyethylene glycol chains. These nanoparticles were employed for the non-covalent surface modification of single walled carbon nanotubes, conferring them magnetic properties. This nanomaterial was employed to immobilize the enzyme xanthine oxidase in order to construct magnetically modified disposable gold screen-printed electrodes as bioelectrodes for the determination of xanthine. The electroanalytical properties of the biosensor were modulated by the nanomaterial composition, being optimal at a carbon nanotubes : magnetic nanoparticles ratio of 1 : 27. The resulting biosensor showed a linear dependence on the xanthine concentration in the 0.25–3.5 μM range with a fast amperometric response in 12 s. The biosensor also showed a noticeable high sensitivity of 1.31 A M−1 cm−2 and a very low detection limit of 60 nM, which can be compared advantageously with other biosensor designs for xanthine.

Nanocrystal Superlattices with Thermally Degradable Hybrid Inorganic−Organic Capping Ligands

Colloidal metallic and semiconductor nanocrystals (NCs) functionalized with metal chalcogenide complexes (MCCs) have shown a promise for designing materials that combine high carrier mobility with the electronic structure of strongly quantum-confined solids. Here we report a simple and general methodology for switching the repulsive forces responsible for colloidal stabilization of MCC-capped NCs from long-range electrostatic to short-range steric through the formation of tight ionic pairs with cationic surfactants. This noncovalent surface modification remarkably improved the ability of MCC-capped NCs to self-assemble into long-range ordered superlattices. These NCs are highly soluble in nonpolar solvents and compatible with various technologically relevant organic molecules and polymers. The hybrid inorganic-organic coating can be thermally decomposed at significantly lower temperatures compared to those required for removal of conventional organic ligands.

Reduction‐Sensitive, Robust Vesicles with a Non‐covalently Modifiable Surface as a Multifunctional Drug‐Delivery Platform

The design and synthesis of a novel reduction-sensitive, robust, and biocompatible vesicle (SSCB[6]VC) are reported, which is self-assembled from an amphiphilic cucurbit[6]uril (CB[6]) derivative that contains disulfide bonds between hexaethylene glycol units and a CB[6] core. The remarkable features of SSCB[6]VC include: 1) facile, non-destructive, non-covalent, and modular surface modification using exceptionally strong host-guest chemistry; 2) high structural stability; 3) facile internalization into targeted cells by receptor-mediated endocytosis, and 4) efficient triggered release of entrapped drugs in a reducing environment such as cytoplasm. Furthermore, a significantly increased cytotoxicity of the anticancer drug doxorubicin to cancer cells is demonstrated using doxorubicin-loaded SSCB[6]VC, the surface of which is decorated with functional moieties such as a folate-spermidine conjugate and fluorescein isothiocyanate-spermidine conjugate as targeting ligand and fluorescence imaging probe, respectively. SSCB[6]VC with such unique features can be used as a highly versatile multifunctional platform for targeted drug delivery, which may find useful applications in cancer therapy. This novel strategy based on supramolecular chemistry and the unique properties of CB[6] can be extended to design smart multifunctional materials for biomedical applications including gene delivery.

Noncovalent Cell Surface Engineering with Cationic Graft Copolymers

Noncovalent Cell Surface Engineering with Cationic Graft Copolymers

The Ubiquitin Binding Region of the Smurf HECT Domain Facilitates Polyubiquitylation and Binding of Ubiquitylated Substrates

Mono- and polyubiquitylation of proteins are key steps in a wide range of biological processes. However, the molecular mechanisms that mediate these different events are poorly understood. Here, we employed NMR spectroscopy to map a non-covalent ubiquitin binding surface (UBS) on the Smurf ubiquitin ligase HECT domain. Analysis of mutants of the HECT UBS reveal that interfering with the UBS surface blocked Smurf-dependent degradation of its substrate RhoA in cells. In vitro analysis revealed that the UBS was not required for UbcH7-dependent charging of the HECT catalytic cysteine. Surprisingly, although the UBS was required for polyubiquitylation of both Smurf itself and the Smurf substrate RhoA, it was not required for monoubiquitylation. Furthermore, we show that mutating the UBS interfered with efficient binding of a monoubiquitylated form of RhoA to the Smurf HECT domain. Our findings suggest the UBS promotes polyubiquitylation by stabilizing ubiquitylated substrate binding to the HECT domain.

Dispersion Behavior of Multi-walled Carbon Nanotubes with Pyrene-Containing Linear and Graft Polymers as Non-covalent Surface Modifiers

Various effects on dispersion of multi-walled carbon nanotubes (MWCNTs) in organic solvent and in polymer film by means of pyrene-containing polymeric surface modifiers were investigated. Graft surface modifiers of poly(ethylene oxide) and of polystyrene with pyrene groups were synthesized by radical co-polymerization of corresponding macromonomers and a pyrene-containing methacrylate monomer. The effect of pyrene content on MWCNT dispersion was examined in THF with polymers of different unit ratio of macromonomer to pyrene monomer. The effect of the polymer architecture was explored with a linear polymer having a pyrene end-group and graft polymers having pyrene units. As a result, the dispersibility of MWCNT in THF was improved with increasing pyrene content in the graft polymer and was also improved by a branched architecture of the polymeric non-covalent surface modifier. Preparation of a homogeneously MWCNT dispersed polystyrene film was investigated with a pyrene-containing graft polystyrene as a compatibilizer between the polystyrene matrix and MWCNT as well.

Noncovalent Cell Surface Engineering with Cationic Graft Copolymers

Chemical approaches to cell surface engineering have emerged as powerful tools for resurfacing the molecular landscape of cells and tissues. Here we report a new strategy for re-engineering cell surfaces through electrostatic adsorption of appropriately structured and functionalized poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) copolymers to cellular interfaces. Grafting of methoxy terminated tetra(ethylene glycol) chains to PLL abrogated polycation cytotoxicity in a charge density and PEG dependent manner, and copolymers structured with a unique balance of grafted PEG chains and free lysine monomers adsorbed to cell surfaces without compromising viability. Structurally analogous PLL-g-PEG copolymers bearing terminally functionalized PEG grafts were used as 'cell surface active' polymeric carriers for biotin, hydrazide, and azide moieties, which selectively captured streptavidin-, aldehyde-, and cyclooctyne-labeled probes, respectively, on cell surfaces. This strategy opens new opportunities in cell surface engineering, including generation of unique cell surface motifs, rapid and combinatorial surface modification, and use of biologically complex solvents. Tailored PLL-g-PEG copolymers offer a promising and enabling tool for bio/chemically remodeling cells and tissues with broad potential in biomedical and biotechnological applications.

Cationic Lipid Formulations Alter the In Vivo Tropism of AAV2/9 Vector in Lung

Physicochemical properties of gene transfer vectors play an important role in both transduction efficiency and biodistribution following airway delivery. Adeno-associated virus (AAV) vectors are currently used in many gene transfer applications; however, the respiratory epithelium remains a challenging target. We synthesized two cationic sterol-based lipids, dexamethasone-spermine (DS) and disubstituted spermine (D(2)S) for pulmonary gene targeting. Scanning and transmission electron micrographs (TEM) confirmed that AAV/lipid formulations produced submicron-sized clusters. When AAV2/9 or AAV2/6.2 were formulated with these cationic lipids, the complexes had positive zeta potential (zeta) and the transduction efficiency in cultured A549 cells increased by sevenfold and sixfold, respectively. Transduction of cultured human airway epithelium with AAV2/6.2-lipid formulations also showed approximately twofold increase in green fluorescence protein (GFP) positive cells as quantified by flow cytometry. Intranasal administration of 10(11) genome copies (GC) of AAV2/9 and AAV2/6.2 coformulated with lipid formulations resulted in an average fourfold increase in transgene expression for both vectors. Formulation of AAV2/9 with DS changed the tropism of this vector for the alveolar epithelium, resulting in successful transduction of conducting airway epithelium. Our results suggest that formulating AAV2/9 and AAV2/6.2 with DS and D(2)S can lead to improved physicochemical characteristics for in vivo gene delivery to lung.

Substantiating in vivo magnetic brain tumor targeting of cationic iron oxide nanocarriers via adsorptive surface masking

Cationic magnetic nanoparticles are attractive as potential vehicles for tumor drug delivery due to their favorable interactions with both the tumor milieu and the therapeutic cargo. However, systemic delivery of these nanoparticles to the tumor site is compromised by their rapid plasma clearance. We developed a simple method for in vivo protection of cationic nanocarriers, using non-covalent surface masking with a conjugate of low molecular weight heparin and polyethylene glycol. Surface masking resulted in a 11-fold increase in plasma AUC and a 2-fold increase in the magnetic capture of systemically injected nanoparticles in orthotopic rodent brain tumors. Overall, the described methodology could expand the prospective applications for cationic magnetic nanoparticles in magnetically mediated gene/drug delivery.

Preparation and Selected Properties of an Improved Composite of the Electrophoretically Deposited Single-Wall Carbon Nanotubes, Electrochemically Coated with a C60-Pd and Polybithiophene Mixed Polymer Film

An improved carbon nanotube conducting composite material for electrochemical capacitors has been devised and tested. It was prepared by electrophoretic deposition of a film of noncovalently surface modified with 1-pyrenebutyric acid HiPCO single-wall carbon nanotubes (pyr-SWCNTs), which were then electrochemically coated, under multiscan cyclic voltammetry (CV) conditions, with a mixed film of the fullerene-palladium (C60-Pd) polymer and the polybithiophene (PBT) polymer. Both the electrophoretic deposition of pyr-SWCNTs and electrochemical polymerization of (C60-Pd)-PBT was in situ monitored by piezoelectric microgravimetry (PM) with the use of an electrochemical quartz crystal microbalance (EQCM). Atomic force microscopy imaging of the film revealed that pyr-SWCNTs formed tangles of pyr-SWCNTs bundles surrounded by globular clusters of (C60-Pd)-PBT. X-ray photoelectron spectroscopy provided information on the mole ratio of BT/C60/Pd ≈ 1:2:4 indicating that, most likely, the C60-Pd and PBT polymers are ...

The effect of the degree of deacetylation of chitosan on its dispersion of carbon nanotubes

The effect of the degree of deacetylation (DD) of chitosan biopolymer on the noncovalent surface modification of multiwall carbon nanotubes (MWCNTs) is presented. MWCNTs were modified by chitosan having different degree of deacetylation (61%, 71%, 78%, 84%, 90% and 93%) and UV–Visible spectroscopy was used to evaluate their dispersion efficiency as a function of chitosan concentration and degree of deacetylation. Results showed that the dispersion of MWCNTs could be dramatically improved when using chitosan with the lowest degree of deacetylation (61%DD) possibly due to a higher surface coverage of the MWCNTs. Zeta potential measurements were used to confirm that the chitosan surface coverage on the MWCNTs was twice as high when modifying the nanotubes surface with the 61%DD than when using the 93%DD chitosan. These results suggest that the dispersion of MWCNTs with chitosan can be improved when using chitosan having a degree of deacetylation of 61%. These results are of interest in particular for the improved dispersion of MWCNTs in aqueous solutions such as in drug delivery applications.

Three dimensional metal pattern transfer for replica molded microstructures

We report a replica molding process for simultaneously forming a three dimensional metal pattern on the surface of molded polymer microstructures. This technique uses noncovalent surface forces to guide the transfer of thin metal films from the three dimensional features of high aspect ratio poly(dimethylsiloxane) micromolds to polymeric replicates. The utility of this technique has been demonstrated by the fabrication of organic coplanar waveguides integrated with vertical Ka-band monopole antenna radiators. These microwave systems show good performance with over 18% bandwidth and greater than 16 dB return loss, demonstrating the versatility of this process.

Surfactant formulations for multi-functional surface modification

Surfactant formulations based on derivatives of Pluronic ® F108 and SDS have been proposed which are capable of modifying polymer surfaces for both biospecific ligand binding and surface regeneration. Planar, non-porous polysulfone, poly(ether imide) and poly(vinylidene fluoride) membranes were fabricated as solid adsorption matrices for non-covalent pluronic surface modification and SDS regeneration. Pluronic surfactants are poly(ethylene oxide) x –poly(propylene oxide) y –poly(ethylene oxide) x (PEO x –PPO y –PEO x ) tri-block copolymers, that self-assemble onto hydrophobic surfaces via the hydrophobic PPO centre block, while the longer hydrophilic PEO chain forms a flexible tether that terminates in a functional hydroxyl moiety. In this study, the terminal hydroxyl group has also been targeted for the covalent attachment of ligands. The amphiphilic non-ionic surfactant pluronic F108, was covalently derivatised to form novel ligands (halide and thiol derivatives for surface analysis), pluronic–biotin as a biochemical sensor and pluronic–DMDDO for metal chelation. The surface functionalised polymers described can also be re-used with an SDS based regeneration formulation.