Protein-resistant and fibrinolytic polyurethane surfaces

Surfaces with resistance to non-specific protein adsorption and a high capacity to bind plasminogen from plasma are developed for application as fibrinolytic surfaces in blood contact. A new method is reported for grafting poly(OEGMA-co-HEMA) copolymers on polyurethane surfaces. The OEGMA provides effective protein resistance due to the PEG side chains and the HEMA provides a high density of OH groups for attachment of lysine. Adsorption of fibrinogen from buffer and plasma to these surfaces is low, indicating significant protein resistance. Plasminogen binding from plasma is high, and clot dissolution on surfaces where plasminogen adsorbed from plasma is converted to plasmin is rapid.     

Phosphonic acid monolayers for binding of bioactive molecules to titanium surfaces

Two different phosphonic acid monolayer films for immobilization of bioactive molecules such as the protein BMP-2 on titanium surfaces have been prepared. Monolayers of (11-hydroxyundecyl)phosphonic acid and (12-carboxydodecyl)phosphonic acid molecules were produced by a simple dipping process (the T-BAG method). The terminal functional groups on these monolayers were activated (carbonyldiimidazole for hydroxyl groups and N-hydroxysuccinimide for carboxyl groups) to bind amine-containing molecules. The reactivity of the surfaces was investigated using trifluoroethylamine hydrochloride and BMP-2. Each step of the surface modification procedure was characterized by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry.     

Interfacing carbon nanotubes with living cells

We developed a polymer coating for carbon nanotubes (CNTs) that mimics the mucin glycoprotein coating of mammalian cells. CNTs coated with these mucin mimic polymers have two novel properties: they can bind to carbohydrate receptors, providing a means for biomimetic interactions with cell surfaces, and, importantly, they are rendered nontoxic to cells.     

Hydrogen activation on Mo-based sulfide catalysts,a periodic DFT study

Hydrogen adsorption on Mo[bond]S, Co[bond]Mo[bond]S, and Ni[bond]Mo[bond]S (10 1 macro 0) surfaces has been modeled by means of periodic DFT calculations taking into account the gaseous surrounding of these catalysts in working conditions. On the stable Mo[bond]S surface, only six-fold coordinated Mo cations are present, whereas substitution by Co or Ni leads to the creation of stable coordinatively unsaturated sites. On the stable MoS(2) surface, hydrogen dissociation is always endothermic and presents a high activation barrier. On Co[bond]Mo[bond]S surfaces, the ability to dissociate H(2) depends on the nature of the metal atom and the sulfur coordination environment. As an adsorption center, Co strongly favors molecular hydrogen activation as compared to the Mo atoms. Co also increases the ability of its sulfur atom ligands to bind hydrogen. Investigation of surface acidity using ammonia as a probe molecule confirms the crucial role of sulfur basicity on hydrogen activation on these surfaces. As a result, Co[bond]Mo[bond]S surfaces present Co[bond]S sites for which the dissociation of hydrogen is exothermic and weakly activated. On Ni[bond]Mo[bond]S surfaces, Ni[bond]S pairs are not stable and do not provide for an efficient way for hydrogen activation. These theoretical results are in good agreement with recent experimental studies of H(2)[bond]D(2) exchange reactions.     

One-step photochemical introduction of nanopatterned protein-binding functionalities to oligo(ethylene glycol)-terminated self-assembled monolayers

Exposure of oligo(ethylene glycol) (OEG)-terminated self-assembled monolayers (SAMs) to UV light leads to the formation of aldehyde groups, leading to a simple one-step method for the introduction of reactive functional groups to protein-resistant surfaces. X-ray photoelectron spectroscopy has been used to demonstrate binding of amines to the modified surfaces, while surface plasmon resonance has shown that proteins are covalently bound. Modified OEG monolayers bind streptavidin at least as well as N-hydroxysuccinimidyl ester functionalized monolayers. Micrometer and nanometer-scale patterns are conveniently fabricated by exposing the monolayers using, respectively, a mask and a scanning near-field optical microscope.     

The thermochemistry of adsorbates on transition metal cluster ions: relationship to bulk-phase properties

In previous work, guided ion beam tandem mass spectrometry has been used to study the reactions of the cluster cations of several transition metals (V, Cr, Fe and Ni) with D2, O2, CO2 and CD4. By examining the kinetic energy dependence of these reactions and interpreting thresholds observed for various reactions, bond energies for D, O, C, CD, CD2 and CD3 can be obtained. The results of these studies are reviewed with an emphasis on the relationship between the thermochemistry obtained from this work with that for adsorbates on bulk-phase metal surfaces. It is found that in cases where quantitative comparison can be made, for example D and O atoms, modest sized clusters bind these species to approximately the same extent as the bulk-phase surface of the same metal. As there is little information available for the molecular fragments investigated here, the cluster bond energies provide some of the first experimental values for such adsorbates on surfaces.     

Modification of polyurethane surface with an antithrombin-heparin complex for blood contact: influence of molecular weight of polyethylene oxide used as a linker/spacer

Polyurethane (PU) was modified using isocyanate chemistry to graft polyethylene oxide (PEO) of various molecular weights (range 300-4600). An antithrombin-heparin (ATH) covalent complex was subsequently attached to the free PEO chain ends, which had been functionalized with N-hydroxysuccinimide (NHS) groups. Surfaces were characterized by water contact angle and X-ray photoelectron spectroscopy (XPS) to confirm the modifications. Adsorption of fibrinogen from buffer was found to decrease by ~80% for the PEO-modified surfaces compared to the unmodified PU. The surfaces with ATH attached to the distal chain end of the grafted PEO were equally protein resistant, and when the data were normalized to the ATH surface density, PEO in the lower MW range showed greater protein resistance. Western blots of proteins eluted from the surfaces after plasma contact confirmed these trends. The uptake of ATH on the PEO-modified surfaces was greatest for the PEO of lower MW (300 and 600), and antithrombin binding from plasma (an indicator of heparin anticoagulant activity) was highest for these same surfaces. The PEO-ATH- and PEO-modified surfaces also showed low platelet adhesion from flowing whole blood. It is concluded that for the PEO-ATH surfaces, PEO in the low MW range, specifically MW 600, may be optimal for achieving an appropriate balance between resistance to nonspecific protein adsorption and the ability to take up ATH and bind antithrombin in subsequent blood contact.     

利用表面上的小分子控制细胞黏附

细胞黏附是重要的生理过程,多细胞生物体中大部分种类的细胞都依赖于在表面的黏附而进行其正常生理活动。细胞的黏附需要固定在表面的有机分子（例如蛋白质或多肽）作配体。我们利用表面小分子模拟蛋白质或多肽作为配体,通过与细胞膜上受体结合,促进细胞黏附到表面。聚乙二醇（PEG）可以抵抗细胞在表面的黏附,我们利用含有PEG的表面小分子来调节细胞黏附。细胞表面的受体与胞外基质表面的配体结合是一个动态过程,在适宜时间和空间发生的时候,细胞就会产生运动和迁移,细胞的迁移也是重要的生理过程。本文主要介绍近年来利用小分子的表面化学和微纳米结构控制细胞在表面的黏附和迁移。     

Single component and selective competitive protein adsorption in a patchy polymer brush: opposition between steric repulsions and electrostatic attractions

This work explores the use of "patchy" polymer brushes to control protein adsorption rates on engineered surfaces and to bind targeted species from protein mixtures with high selectivity but without invoking molecular recognition. The brushes of interest contain embedded cationic "patches" composed of isolated adsorbed poly(l-lysine) coils (PLL) that are about 10 nm in diameter and are randomly arranged on a silica substrate. Around these patches is a protein-resistant poly(ethylene glycol) (PEG) brush that is formed from the adsorption of a PLL-g-PEG graft copolymer on the remaining silica surface. Electrostatic attractions between individual cationic patches and the negative regions of approaching proteins may be energetically insufficient to bind proteins. Furthermore, protein-patch attractions are reduced by steric repulsions between proteins and the PEG brush. We show that protein adsorption, gauged by ultimate short-term coverages and by the initial protein adsorption rate, exhibits an adhesion threshold: pure PEG brushes of the architectures employed here and brushes containing sparse loadings of PLL patches do not adsorb protein. Above a critical PLL patch loading or threshold, protein adsorption proceeds, often dramatically. The PLL patch thresholds are specific to the protein of interest, allowing surfaces to be engineered to adhesively discriminate different proteins within a mixture. The separation achieved is remarkably sharp: one protein adsorbs, but the second is completely rejected from the interface. The surfaces in this study, by virtue of their well-controlled and well-characterized patchy nature, distinguish themselves from multicomponent brushes or brushes used to end-tether peptide sequences and nucleotides.     

Surface diffusion as a rate-enhancing mechanism in macromolecular association: The effectiveness of one- and two-dimensional surface sliding

The effective rate for a macromolecular association can be increased if the molecules can be held together loosely by nonspecific surface forces while they search for the specific reactive sites. In this way steric constraints can be relieved. In extreme cases, a specific interaction site can be surrounded by extensive surfaces either essentially linear (e.g. a DNA site) or two-dimensional (e.g. a membrane-bound receptor). If ligands can bind nonspecifically and search these surfaces in a lower-dimensional diffusion process, very substantial rate enhancements can be achieved under suitable conditions. The ranges of concentration and affinity of such nonspecific surfaces that can produce rate enhancements are derived and discussed. It is found that under the expected conditions in the living cell, such rate enhancements will be fairly modest. Nonetheless, nonspecific surface diffusion may play an important role.     

Supramolecular binding of cationic porphyrins on a filamentous bacteriophage template: toward a noncovalent antenna system

Engineered viruses act as scaffolds to bind porphyrins on their surfaces, exploiting mainly electrostatic interactions. The close proximity between porphyrins and tryptophan residues, exposed on the solvent-accessible surface, leads to an efficient resonant energy transfer, which makes these systems suitable for developing noncovalent antenna systems.     

Cover Picture

The cover picture shows the process of building functional amphiphilic protein-polymer hybrids in a modular fashion. Monolayers of biotinylated polystyrene (purple) bind the protein streptavidin (blue), resulting in the formation of giant amphiphiles. The remaining free binding sites are subsequently used to associate biotinylated biomacromolecules (yellow), such as the iron-storage protein ferritin. The use of covalent conjugates of streptavidin and horseradish peroxidase leads to the formation of reactive surfaces, which are capable of catalyzing organic reactions. Further details on these giant amphiphiles are reported by Nolte and co-workers on p. 4732 ff.     

Nanoscale probing of the enamel nanorod surface using polyamidoamine dendrimers

Although it is known that noncollagenous proteins of dental origin bind to the hydroxyapatite crystal surfaces, no measure of their binding strength has been calculated. This experiment used -COOH-capped generation 7 PAMAM dendrimers as nanoprobes of the biological hydroxyapatite nanorod surfaces. Dendrimer distribution was characterized using AFM. The results showed dendrimers to be spaced at intervals along the c-axis of the crystals. From these observations and assuming a fully ionized -COOH dendrimer, a mathematical model of the binding capacity of the crystal surface with the dendrimer was developed. The Monte Carlo method was used to simulate the binding process between the dendrimer and crystal surface, and the binding strength of the -COOH groups to the surface was calculated to be 90 +/- 20 kJ/mol. These results support the CFM studies which have described alternating bands of charge domains on the crystal surface and that the binding strength will be dependent on both the intensity of the charge on the protein and the crystal surface.     

Synthesis of functional monolayer surfaces for rapid radiometric determination of plutonium

Glass or silicon substrates functionalized with a monolayer of carbamoylmethylphosphonate (CMP) ligands effectively bind tetravalent actinides from optimized mineral acid solutions to enable rapid, high quality radiometric assay by alpha spectrometry. The observed alpha spectra compare favorably with the highest quality electroplated samples. The CMP-functionalized surfaces have been used to develop simplified analytical methods to determine plutonium from complex mixtures.     

Diffusion and elementary atomic processes at steeped surfaces

The mobility of atoms at and near lattice step edges plays an important role in epitaxial growth and surface morphology of thin films, and the dynamic behavior of surfaces at elevated temperature. We summarize our recent FIM studies on how atoms move and bind at step edges, how atoms can descend and ascend lattice steps, how in-layer atoms can move up to the upper terrace, and how these atomic processes are related to various growth structures in thin film epitaxy.     

Extending foldamer design beyond α-helix mimicry: α/β-peptide inhibitors of vascular endothelial growth factor signaling

Diverse strategies have been explored to mimic the surface displayed by an α-helical segment of a protein, with the goal of creating inhibitors of helix-mediated protein-protein interactions. Many recognition surfaces on proteins, however, are topologically more complex and less regular than a single α-helix. We describe efforts to develop peptidic foldamers that bind to the irregular receptor-recognition surface of vascular endothelial growth factor (VEGF). Our approach begins with a 19-residue α-peptide previously reported by Fairbrother et al. (Biochemistry 1998, 37, 17754) to bind to this surface on VEGF. Systematic evaluation of α→β replacements throughout this 19-mer sequence enabled us to identify homologues that contain up to ~30% β residues, retain significant affinity for VEGF, and display substantial resistance to proteolysis. These α/β-peptides can block VEGF-stimulated proliferation of human umbilical vein endothelial cells.     

Combined use of lectin affinity chromatography and endo-beta-galactosidase to study polylactosamine sequences isolated from haemopoietic cell surfaces

The trypsin-sensitive glycopeptides from cell surfaces of a multipotential murine haemopoietic cell line (DE) have been studied using serial lectin affinity chromatography on columns of immobilized lentil lectin (LCA), concanavalin A (Con A), and wheat-germ agglutinin (WGA). WGA-binding material consisted of glycopeptides that failed to bind to LCA and Con A. Step elution from the WGA-column with 0.01-, 0.1-, 0.5- and 1.0 M N-acetyl-D-glucosamine yielded four affinity classes of glycopeptide (WGA-W, WGA-I, WGA-S and WGA-SS respectively). WGA-W, WGA-I and WGA-S contained both alkali-stable (N-linked) and alkali-labile (O-linked) carbohydrate on high molecular weight glycopeptides. The WGA-SS fraction contained only N-linked carbohydrate. N-linked glycopeptides isolated from each WGA-binding class differed in molecular size, relative N-acetylneuraminic acid content and affinity for Ricinus communis 120 agglutinin. endo-beta-Galactosidase digestion showed that these glycopeptides contained polylactosamine-type glycans. Gel filtration profiles of the enzyme treated materials were different for each WGA-binding population suggesting variation in branching patterns and/or substitution with fucose residues. Affinity chromatography has shown that the WGA binding molecules are the major glycopeptide group at DE cell surfaces.     

An Electron‐Rich Cyclic (Alkyl)(Amino)Carbene on Au(111), Ag(111), and Cu(111) Surfaces

The structural properties and binding motif of a strongly σ‐electron‐donating N‐heterocyclic carbene have been investigated on different transition‐metal surfaces. The examined cyclic (alkyl)(amino)carbene (CAAC) was found to be mobile on surfaces, and molecular islands with short‐range order could be found at high coverage. A combination of scanning tunneling microscopy (STM), X‐ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculations highlights how CAACs bind to the surface, which is of tremendous importance to gain an understanding of heterogeneous catalysts bearing CAACs as ligands.     

A Protein‐Resistant Matrix for Electrochemical Based Recognition Assays

In this work, two well known polymers, carboxymethyl dextran and poly(ethyleneglycol), are used for easily producing a platform for electrochemical affinity assays, avoiding nonspecific adsorption of proteins. In this way, modified electrode surfaces able to bind a recognition agent are constructed through simple and reliable reactions.