Search

Fungal hyphae deeply invade the cornea in fungal keratitis. The corneal stroma hinders the infiltration of antifungal drugs and reduces their bioavailability. Here we report a peptide conjugate nano-assembly that permeates the stroma and kills the pathogen without irritating the ocular cornea. The hydrophilic surface of the nano-assembly ensures deep permeation into the stroma. When encountering a fungal hyphal cell, the nano-assembly disassembles and exposes the α-helical peptide to destroy the fungal membrane, thus inactivating the pathogen. In a rabbit model of fungal keratitis, the nano-assembly exhibits a better therapeutic effect than commercially available natamycin ophthalmic suspension. Peptide conjugates with a nano-assembled structure and assembly-disassembly behavior could serve as the foundation of a new therapy for fungal keratitis. This article is protected by copyright. All rights reserved.

3-dimensional (3D) bioprinting technology provides promising strategy in the fabrication of artificial tissues and organs. As the fundamental element in bioprinting process, preparation of bioink with ideal mechanical properties without sacrifice of biocompatibility is a great challenge. In this study, a supramolecular hydrogel-based bioink is prepared by polyethylene glycol (PEG) grafted chitosan, α-cyclodextrin (α-CD) and gelatin. It has a primary crosslinking structure through the aggregation of the pseudo-polyrotaxane-like side chains, which are formed from the host-guest interactions between α-CD and PEG side chain. Apparent viscosity measurement shows the shear-shinning property of this bioink, which might be due to the reversibility of the physical crosslinking. Moreover, with β-glycerophosphate at different concentrations as the secondary crosslinking agent, the printed constructs demonstrate different Young's modulus (p, Graphical abstract Image 1, Highlights • Supramolecular bioink demonstrates good shear-shinning property. • Dual crosslinking provides the bioink with tunable strength. • Tunable strength facilitates stem cells lineage differentiation.

Pseudomonas aeruginosa (P. aeruginosa) biofilms are associated with a wide range of infections, from chronic tissue diseases to implanted medical devices. In a biofilm, the extracellular polymeric substance (EPS) causes an inhibited penetration of antibacterial agents, leading to a 100-1000 times tolerance of the bacteria. In view of the water-filled channels in biofilms and the highly negative charge of EPS, we design a chitosan-polyethylene glycol-peptide conjugate (CS-PEG-LK13) in this study. The CS-PEG-LK13 prefers a neutrally charged assembly at a size of ∼100 nm in aqueous environment, while undergoes disassembly to expose the α-helical peptide at the bacterial cell membrane. This behavior provides CS-PEG-LK13 superiorities in both penetrating the biofilms and inactivating the bacteria. At a concentration of 8 times the minimum inhibitory concentration, CS-PEG-LK13 has a much higher antibacterial efficiency (72.70%) than LK13 peptide (15.24%) and tobramycin (33.57%) in an in vitro P. aeruginosa biofilm. Moreover, CS-PEG-LK13 behaves comparable capability of combating an implanted P. aeruginosa biofilm to highly excess tobramycin. This work has implications for the design of new antibacterial agents in biofilm combating.

As a typical plant virus which has biocompatibility and high transfection efficiency, tobacco mosaic virus (TMV) has shown broad application potential in drug or gene delivery field. Elucidating its intracellular trafficking is of great importance in investigation of its cytotoxicity, targeting site, and delivery efficiency, and is advantageous to designing new TMV-based drug delivery systems with different targets. By taking advantage of the regulated pH value of different organelles in a mammalian cell, we exploit a pH detection strategy to investigate the intracellular trafficking pathway of TMV. Here, we report a single-wavelength excited ratiometric fluorescent pH probe. This probe is constructed by simultaneously coupling pH-sensitive fluorescein isothiocyanate (FITC) and pH-insensitive rhodamine B isothiocyanate (RBIRC) onto the inner surface of TMV. The fluorescence intensity ratio of FITC to RBITC excited at 488 nm responds specifically towards pH value over other interferential agents. By taking use of this single-wavelength excited ratiometric pH probe and confocal laser scanning microscopy, it is shown that the endocytosed TMV is located in a pH decreasing microenvironment and eventually enters lysosomes. This work may provide important guidance on construction of TMV-based nano carriers.

Antibiotic resistance has become one of the major threats to global health. Photodynamic inactivation (PDI) develops little antibiotic resistance; thus, it becomes a promising strategy in the control of bacterial infection. During a PDI process, light-induced reactive oxygen species (ROS) damage the membrane components, leading to the membrane rupture and bacteria death. Due to the short half-life and reaction radius of ROS, achieving the cell-membrane intercalation of photosensitizers is a key challenge for PDI of bacteria. In this work, a tetraphenylethylene-based discrete organoplatinum(II) metallacycle (1) acts as a photosensitizer with aggregation-induced emission. It self-assembles with a transacting activator of transduction (TAT) peptide-decorated virus coat protein (2) through electrostatic interactions. This assembly (3) exhibits both ROS generation and strong membrane-intercalating ability, resulting in significantly enhanced PDI efficiency against bacteria. By intercalating in the bacterial cell membrane or entering the bacteria, assembly 3 decreases the survival rate of gram-negative Escherichia coli to nearly zero and that of gram-positive Staphylococcus aureus to ∼30% upon light irradiation. This study has wide implications from the generation of multifunctional nanomaterials to the control of bacterial infection, especially for gram-negative bacteria.

Phenotype conversion of smooth muscle cells (SMCs) plays a key role in the formation of atherosclerosis. Understanding how SMCs respond to a micro/nano-topology and elucidating the cellular mechanism of phenotype conversion is critical to the atherosclerosis treatment. Herein, we prepared poly(ɛ-caprolactone) (PCL) spherulites with a radius more than 350 μm for the studying of radial microstructure influence on SMCs behaviors. We found that on the PCL spherulitic films, SMCs grew aligning the radial direction of PCL spherulites, overexpressed α-SMA gene than OPN gene, and preferred contractile phenotype. FAK signaling pathway and ROCK1 signaling pathway both contributed to the contractile phenotype maintenance of SMCs. This work illustrated the feasibility of spherulites in regulating SMCs behaviors, and elucidated the mechanism how SMCs respond to a radial micro/nano-topology. This research may provide theoretical basis for the atherosclerosis formation and treatment.

In order to combat antibiotic resistance, the development of new antibacterial agents is essential. In this study, we prepared four types of amino acid modified chitosan (CS-AA). Compared with chitosan modified with hydrophobic amino acids, the chitosan modified with positively charged amino acids showed higher antibacterial efficiency against Escherichia coli (E. coli) under similar grafting rate. CS-AA achieves antibacterial properties mainly by destroying the integrity of bacterial cell membranes. All the four types of CS-AA show low toxicity towards red blood cells. This work indicates that positively charged groups are more important than hydrophobic groups in the design of chitosan-based antibacterial agents, and provides helpful information for the molecular design of effective antibacterial agents.

Gram-negative bacteria, which possess an impermeable outer membrane, are responsible for many untreatable infections. The lack of development of new relevant antibiotics for over 50 years has increased threats. Peptides are regarded as the most promising alternatives to antibiotics. However, since the activities of existing peptides are not yet comparable to those of current antibiotics, there is an urgent need to improve their antibacterial efficiencies. Herein, we conjugate peptides onto one-dimensional rod-like tobacco mosaic virus (TMV). The peptides on the obtained nanoparticles (peptide-TMV) are hundreds of times superior to free peptides in combating Gram-negative bacteria. Through morphology and gene detection of Escherichia coli, it was revealed that following peptide-TMV application, the high osmotic pressure related to membrane damage and the generated reactive oxygen species cause Escherichia coli's death. In addition, peptide-TMV causes a downregulation of biofilm-related genes, inhibiting biofilm formation. This work paves the way to combat Gram-negative bacteria-related infection.

Infection control and the promotion of healing are two key factors during the wound repair process. However, it is still a major challenge for one material to inhibit bacterial growth efficiently and promote wound healing at the same time. Here, a bifunctional chitosan derivative (CS-G/mPEG) was prepared by the successive modification of chitosan with carboxymethoxypolyethylene glycol (mPEG-COOH) and aminoiminomethanesulfonic acid (AIMSOA). We demonstrated that CS-G/mPEG can selectively disrupt bacterial membranes with high efficiency and thus kill Gram-positive bacteria without inducing hemolysis or cytotoxicity. In rats with full-thickness skin wounds infected with Staphylococcus aureus bacteria, CS-G/mPEG inhibited the growth of the bacteria and accelerated the healing of the wounds. Owing to the balance between the antimicrobial activity and biological safety of CS-G/mPEG, this bifunctional chitosan derivative is promising as an ideal anti-infective wound-repairing material for managing wounds with Gram-positive bacterial infections.

We present here that pyrene derivative can be arranged in close proximity using M13 virus as framework through click reaction. The observation of excimer emissions of pyrene was a direct evidence for the proper spatial arrangements of chromophores in the architecture, in which both ground-state and excited-state electronic interactions of pyrenes were facilitated. Efficient energy transfer could be induced through the electrostatic interactions between the M13 backbone and the positively charged rhodamine 6G. The investigation of chromophore-modified M13 and its energy transfer process would be beneficial for exploiting the structures of various natural virus and artificially self-assembled virus-like particles.

Tobacco mosaic virus coat protein was modified with a small molecular fluorous ponytail at specific sites, and self-assembled into spherical nanoparticles through fluorous interaction induced self-assembly. By loading the anti-cancer drug cisplatin through metal-ligand coordination, this spherical assembly with high stability has potential as a drug carrier.

Hydrogen-bonded supramolecular polymer nanoparticles (SPNPs), serving as a ratiometric oxygen nanoprobe for hypoxia sensing and photodynamic therapy (PDT) treatment, were designed. Herein, oxygen-sensitive phosphorescent Pt(II) porphyrin moiety and oxygen-insensitive fluorescent 9,10-diphenylanthracene moiety were assembled through quadruple hydrogen bonding into SPNPs. The efficient energy transfer between the monomeric donor–acceptor pairs in the SPNPs leads to enhanced phosphorescence with long lifetimes. The resulting bright phosphorescence can realize hypoxia sensing in living cells and generate singlet oxygen efficiently in SPNPs to kill cancer cells. This is the first example of a multi-functional supramolecular polymer-based nanoprobe for ratiometric hypoxia sensing, imaging and PDT treatment.

One-dimensional (1D) hybrid nanofibers with surface-deposited gold nanoparticles (AuNPs) have been fabricated by self-assembly of rod-like tobacco mosaic virus (TMV) with mussel-inspired polymerization of dopamine and in situ reduction of gold ion, providing a method for sensing the endocytic pathway of nanomaterial.

The emergence of drug resistant bacterium threatens the global public healthcare systems. The urgent need to obtain new antimicrobials has driven antimicrobial peptides (AMPs) research into spotlight. Here we give a brief introduction of the recent progress of AMPs regarding their structures, properties, production and modification, and antimicrobial mechanism. Thereby, this review will give an insight into the trends and challenges facing on this particular kind of antimicrobial materials.

Plant viruses have been applied broadly in nanomedical applications profiting from their monodisperse structure, biocompatibility, easy modification, and non-pathogenicity in animals. Here we report a tobacco mosaic virus (TMV) based drug delivery system bearing carbohydrates as targeting ligands. Mannose (Man) and lactose (Lac) moieties were separately conjugated to the exterior surface of TMV (TMV-Man and TMV-Lac) through an efficient copper(i)-catalyzed azide-alkyne cycloaddition. Cisplatin (CDDP), an anticancer drug, was directly loaded into the TMV cavity (CDDP@TMV, CDDP@TMV-Man and CDDP@TMV-Lac) via a metal coordination bond. Through the specific recognition between carbohydrates and glycoproteins in cell membranes, these TMV based vectors show specificity in different cell lines: in the galectin-rich MCF-7 cell line, CDDP@TMV-Man shows enhanced endocytosis and apoptosis efficiency; in the asialoglycoprotein receptor (ASGPR)-overexpressing HepG2 cell line, CDDP@TMV-Lac shows superiority in endocytosis and apoptosis. This research provides a new strategy for tumor-targeted cisplatin delivery.

For cancer therapy, viruses have been utilized as excellent delivery vehicles because of their facile transfection efficiency in their host cells. However, their inherent immunogenicity has become the major obstacle for their translation into approved pharmaceuticals. Herein, we utilized rodlike plant virus, tobacco mosaic virus (TMV), which is nontoxic to mammals and mainly infects tobacco species, as anticancer nanorod-drug vector for cancer therapy study. Doxorubicin (DOX) was installed in the inner cavity of TMV by hydrazone bond, which enabled the pH-sensitive drug release property. Conjugation of cyclic Arg-Gly-Asp (cRGD) on the surface of TMV can enhance HeLa cell uptake of the carrier via the integrin-mediated endocytosis pathway. Comparing with free DOX, the cRGD-TMV-hydra-DOX vector had similar cell growth inhibition and much higher apoptosis efficiency on HeLa cells. Moreover, the in vivo assay assumed that cRGD-TMV-hydra-DOX behaved similar antitumor efficiency but much lower side effect on HeLa bearing Balb/c-nu mice. Our work provides novel insights into potentially cancer therapy based on rodlike plant viral nanocarriers.

Phenotype conversion of smooth muscle cells (SMCs) plays a key role in the formation of atherosclerosis. Understanding how SMCs respond to a micro/nano-topology and elucidating the cellular mechanism of phenotype conversion is critical to the atherosclerosis treatment. Herein, we prepared poly(

Inspired by the high gene transfer efficiency of viral vectors and to avoid side effects, we present here a 1D rod-like gene-silencing vector based on a plant virus. By decorating the transacting activator of transduction (TAT) peptide on the exterior surface, the TAT-modified tobacco mosaic virus (TMV) achieves a tunable isoelectric point (from ∼3.5 to ∼9.6) depending on the TAT dose. In addition to enhanced cell internalization, this plant virus-based vector (TMV-TAT) acquired endo/lysosomal escape capacity without inducing lysosomal damage, resulting in both high efficiency and low cytotoxicity. By loading silencer green fluorescent protein (GFP) siRNA onto the TMV-TAT vector (siRNA@TMV-TAT) and interfering with GFP-expressing mouse epidermal stem cells (ESCs/GFP) in vitro, the proportion of GFP-positive cells could be knocked down to levels even lower than 15% at a concentration of ∼100% cell viability. Moreover, by interfering with GFP-expressing highly metastatic hepatocellular carcinoma (MHCC97-H/GFP) tumors in vivo, treatment with siRNA@TMV-TAT complexes for 10 days achieved a GFP-negative rate as high as 80.8%. This work combines the high efficiency of viral vectors and the safety of nonviral vectors and may provide a promising strategy for gene-silencing technology.

Rod-like nanoparticles show unique self-assembly behavior benefiting from their anisotropic properties. As a classic example of a one-dimensional (1D) rod-like plant virus, tobacco mosaic virus (TMV) can either assemble in a head-to-tail manner to form 1D long fibers, or align parallel to form crystal-like structures at interfaces or in solution. Here, the self-assembly behaviors of TMV at oil-water or air-liquid interfaces are summarized. In addition, the self-assembly of TMV with polymers in solution is also discussed in this chapter.

Rod-like nanoparticles show unique self-assembly behavior benefiting from their anisotropic properties. As a classic example of a one-dimensional (1D) rod-like plant virus, tobacco mosaic virus (TMV) can either assemble in a head-to-tail manner to form 1D long fibers, or align parallel to form crystal-like structures at interfaces or in solution. Here, the self-assembly behaviors of TMV at oil-water or air-liquid interfaces are summarized. In addition, the self-assembly of TMV with polymers in solution is also discussed in this chapter.

A ratiometric, multifunctional nanoprobe was prepared consisting of a self-assembled polymeric micelle as the carrier, tetraphenylethene (TPE) as the donor, fluorescent boronate as the H2O2-responsive acceptor, and triphenylphosphonium as a mitochondria-targeted moiety. The assembled nanoparticles could detect both exogenous and endogenous mitochondrial H2O2 changes in living cells.

Pickering emulsion constructions on nanorods with high aspect ratio are a great challenge because of the geometry restrictions. On the basis of the theory that the stability of Pickering emulsion is highly dependent on the size and amphiphilicity of the nanoparticle at fluid interfaces, we report a novel strategy to fabricate long-time stable Pickering emulsion consisting of tobacco mosaic virus (TMV)-like nanorods through the programming self-assembly of TMV coat protein (TMVCP). The first step is the self-assembly of amphiphilic TMVCP at Pickering emulsion interfaces, and the second step is the in situ interfacial self-assembly of TMVCP into nanorods with increased particle size. The robust capsules can be further fabricated through cross-linking of the proteins. By taking advantage of both the amphiphilicity of TMVCP and the subsequent size growth induced by TMVCP self-assembly, this work provides a powerful strategy for constructing robust capsules consisting of nanorods with high aspect ratio, which may show potential applications for drug delivery and virus recognition.

The doping of nitrogen into carbon quantum dots is vitally important for improved fluorescence performance. However, the synthesis of nitrogen-doped carbon quantum dots (N-CQDs) is usually conducted under strong acid and high temperature, which results in environmental pollution and energy consumption. Herein, the N-CQDs were prepared by a mild one-pot hydrothermal process. The hydrothermal reaction temperature was adjusted to control the particle size, nitrogen/carbon atomic ratio, and quantum yield. The products were water soluble with a narrow particle size distribution and good dispersion stability over a wide pH range. The N-CQDs could penetrate into the HeLa cell nucleus without any further functionalization. Moreover, the fluorescence of N-CQDs could be selectively quenched by Cu2+ , which suggested applications for the detection of Cu2+ in human plasma.

Viral nanoparticles have attracted extensive research interests in diverse applications of diagnosis and therapy. In particular, filamentous M13 bacteriophages have shown great potential in biomedical applications. However, its pathways entering into cells still remain unclear, and this greatly hinders its further use as a drug or gene carrier. Here, a ratiometric M13 pH probe is designed by conjugating two fluorescent dyes onto the surface of M13. Since the intensity ratio is not influenced by probe concentration, ion strength, temperature, photobleaching, and optical path length, this ratiometric probe can be used to investigate the intracellular pH map of M13. More importantly, the internalization mechanism of M13 can be elucidated. It is found that this filamentous phage shows great cell-type dependence in interaction with cells and internalization mechanism. The phage tends to be bounded on the cell membrane of only epithelial cells, not endothelial cells. Furthermore, the M13 phage enters into cells through endocytosis with specific mechanism: clathrin-mediated endocytosis and macropinocytosis for HeLa; vesicular transport, clathrin-mediated endocytosis, and macropinocytosis for MCF-7; caveolae-mediated endocytosis for human dermal microvascular endothelial cell (HDMEC). This work provides key notes for cancer diagnosis and therapy based on filamentous bacteriophage, especially for design of pH-sensitive drug delivery systems.

Herein, we show that rod-like tobacco mosaic virus (TMV) can self-assemble into 3D bundled structures in aqueous solution using azobenzene modified Pluronics F127 block copolymers (Azo-F127) to induce depletion. The structures are characterized by both transmission electron microscopy and dynamic light scattering. The self-assembly process can be controlled reversibly by temperature. The formation of Azo-F127 hard spheres during the self-assembly is the main cause of this phenomenon.

On the basis of terminal group electrostatic interactions (TGEI), a supra-amphiphile is formed between a homopolymer of polylactic acid with carboxyl group at one end (PLA-COOH) and hepta-6-hydrazyl-β-cyclodextrin (HH-CD). The amphiphile can self-assemble into a micellar structure in aqueous solution. The outer surface of the micelle, which is composed of cyclodextrins, can be further modified via host-guest interactions. Considering the biocompatibility of the building blocks, the application of the micelles in a nanocarrier of anticancer drugs is further explored.

This study reports a facile method for the synthesis of multi-enzyme co-embedded organic-inorganic hybrid nanoflowers, using glucose oxidase (GOx) and horseradish peroxidase (HRP) as the organic components, and Cu3(PO4)2 · 3H2O as the inorganic component. The synthesized nanoflowers enable the combination of a two-enzyme cascade reaction in one step, in which the GOx component of the nanoflowers oxidizes glucose to generate H2O2, which then reacts with the adjacent HRP component on the nanoflowers to oxidize the chromogenic substrates, resulting in an apparent color change. Given the close proximity of the two enzyme components in a single nanoflower, this novel sensor greatly reduces the diffusion and decomposition of H2O2, and greatly enhances the sensitivity of glucose detection. Thus, the obtained multi-enzyme co-embedded organic-inorganic hybrid nanoflowers can be unquestionably used as highly sensitive colorimetric sensors for the detection of glucose. Notably, this work presents a very facile route for the synthesis of multi-enzyme co-embedded nanomaterials for the simultaneous catalysis of multi-step cascade enzymatic reactions. Furthermore, it has great potential for application in biotechnology, and biomedical and environmental chemistry.

We investigated the effect of amphiphilic Laponite nano-discs, which were edge-modified by hydrophobic chains, on the properties of Pickering emulsions and Pickering emulsions polymerization. Comparing to unmodified Laponites, these amphiphilic nano-discs can greatly reduce the surface tension, resulting in very stable Pickering emulsions. These particles uniquely combine the Pickering effect with amphiphilic properties similar to the surfactant. Taking advantage of these amphiphilic Pickering emulsifiers, miniemulsion polymerization of styrene was performed. Homogeneous polystyrene nanoparticles with size around 150 nm could thus be prepared.

A facile method to prepare monodisperse speckled colloids has been developed via one-step seeded polymerization from noncross-linked latex particles. It was found that both cross-linking agents in the added monomer mixture and charged initiation species are essential for the formation of speckles on composite latex particle surface in seeded polymerization. The size and number density of speckles on the surface are tunable by adjusting the concentration of surfactant. A possible mechanism for the formation of such speckled colloids has been proposed based on a series of control experiments. Speckled colloidal particles were used as substrates for the adsorption of tobacco mosaic virus, and a much stronger adsorption was observed compared to smooth particles, implying a potential application of these speckled particles in virus collection and more.

Polymer fibers composed of poly(ethylene oxide) (PEO) and nanoclay were fabricated by electrospinning. The morphology of the composite nanofibers was characterized by scanning electron microscope (SEM) and transmission electron microscope (TEM), which showed aligned nanoclays in the fibers. Polarized Fourier transform infrared (FT-IR) spectroscopy revealed that the PEO chains in the composite fibers exhibit a higher degree of orientation than that in PEO nanofibers containing no nanoclay. It is believed that spatial confinement is present in the electrospun nanofibers, which results in the enforcement of the mutual restriction. The anisotropic hierarchical nanostructure may have potential applications in optics, mechanical materials, and biomedical materials for cell culture.

Here we report that the rod-like tobacco mosaic virus (TMV), having a negatively charged surface, can be assembled into three-dimensional micrometer-sized bundle-like superstructures via multiple electrostatic interactions with a positively charged molecular "glue", namely, a tetraphenylethylene (TPE)-based discrete organoplatinum(II) metallacycle (TPE-Pt-MC). Due to the nanoconfinement effect in the resultant TMV/TPE-Pt-MC complexes and the aggregation-induced emission (AIE) activity of the TPE units, these hierarchical architectures result in a dramatic fluorescence enhancement that not only provides evidence for the formation of novel metal-organic biohybrid materials but also represents an alternative to turn-on fluorescence. Moreover, the dissociation of these final constructs and subsequent release of individual virus have been achieved by disrupting the TPE-Pt-MC core using tetrabutylammonium bromide (TBAB). This strategy is also compatible with other protein-based nanoparticles such as bacteriophage M13 and ferritin, proving the generality of this approach. Hence, this research will open new routes for the fabrication of functional biohybrid materials involving metal-organic complexes and anisotropically shaped bionanoparticles.

Efficient delivery of therapeutic proteins to a target site remains a challenge due to rapid clearance from the body. Here, we selected tobacco mosaic virus (TMV) as a model protein system to investigate the interactions between the protein and a nonionic block copolymer as a possible protecting agent for the protein. By varying the temperature, we were able to obtain core-shell structures based on hydrophobic interactions among PO blocks and noncovalent interactions between TMV and EO blocks. The protein-polymer interactions were characterized by dynamic light scattering and isothermal titration calorimetry. This study establishes principles for the possible design of clinically useful protein delivery systems.

Viruses, as typical bionanoparticles from nature, possess many superb properties, such as exquisite symmetry, uniformity of size and shape, well-characterized surface chemistry that governs the potential interparticle interactions. These features make viral particles ideal building blocks for self-assembly studies and novel materials development. This review outlines some of the recent research activities in the area of controlled self-assembly of viruses and its potential use as materials. One particular application of the assembled viruses, especially for biomaterials, is also briefly discussed.

Topographical features ranging from micro- to nanometers can affect cell orientation and migratory pathways, which are important factors in tissue engineering and tumor migration. In our previous study, a convective assembly of bacteriophage M13 resulted in thin films which could be used to control the alignment of cells. However, several questions regarding its underlying reasons to dictate cell alignment remained unanswered. Here, we further study the nanometer topographical features generated by the bacteriophage M13 crystalline film, which results in the alignment of the cells and extracellular matrix (ECM) proteins. Sequential imaging analyses at micro- and nanoscale levels of aligned cells and fibrillar matrix proteins were documented using scanning electron microscopy and immunofluorescence microscopy. As a result, we observed baby hamster kidney cells with higher degree of alignment on the ordered M13 substrates than NIH-3T3 fibroblasts, a difference which could be attributed to the intrinsic nature of the cells' production of ECM proteins. The results from this study provide a crucial insight into the topographical features of a biological thin film, which can be utilized to control the orientation of cells and surrounding ECM proteins.

We explore two-dimensional self-assembly of tobacco mosaic viruses (TMVs) on a substrate-supported, fluid lipid monolayer by manipulating the electrostatic interactions, with specific focus on the effects of the cationic lipid concentration in the monolayer and the presence of Ca{sup 2+} ions in the surrounding bulk solution. The TMV assemblies were characterized by grazing-incidence X-ray scattering and atomic force microscopy, and the inter-particle interaction quantified through X-ray scattering data analysis. In the absence of Ca{sup 2+} ions, we found that higher charge densities on the lipid monolayer led to poorer in-plane order, which may be attributed to faster adsorption kinetics, due to the surface potential that increases with charge density. At the same time, higher lipid-charge densities also resulted in weaker repulsion between TMVs, due to partial screening of Coulomb repulsion by mobile cationic lipids in the monolayer. The lipid-charge dependence was diminished with increasing concentration of Ca{sup 2+} ions, which also led to tighter packing of TMVs. The results indicate that Ca{sup 2+} ions strengthen the screening of Coulomb repulsion between TMVs and consequently enhance the role of attractive forces. Control experiments involving Na{sup +} ions suggest that the attractive inter-TMV interaction has contributions from both the van der Waalsmore » force and the counter-ion-induced attraction that depends on ion valence.« less

A facile approach to assembled virus film with tunable structure is presented. Rod-like tobacco mosaic virus (TMV) was selected as the prototype in this study for its anisotropic structural feature. TMV can either “lie down” or “stand up” on gold substrate by tuning the solution pH. A quartz crystal microbalance with dissipation monitoring was used to monitor the pH-dependent self-assembly behavior of TMV nanoparticles, and atomic force microscopy and single molecule force spectroscopy further confirmed the different assembly structures.

A method for site-specific and high yield modification of tobacco mosaic virus coat protein (TMVCP) utilizing a genetic code expanding technology and copper free cycloaddition reaction has been established, and biotin-functionalized virus-like particles were built by the self-assembly of the protein monomers.

Die Schaffung neuer multifunktionaler Materialien mit hierarchischer Ordnung ist ein Schwerpunkt der aktuellen Material- und Ingenieurswissenschaften. Ideale Ansatzpunkte fur diese Bestrebungen sind Luft-Flussigkeit-Grenzflachen und Grenzflachen zwischen zwei Flussigkeiten, an denen sich Nanopartikel oder kolloidale Partikel akkumulieren und selbstorganisieren konnen. An solchen fluiden Grenzflachen wurden bereits verschiedenste Organisationsprozesse und Reaktionen durchgefuhrt, um hierarchische Strukturen wie zweidimensionale kristalline Filme, Kolloidosome, “Himbeer”-ahnliche Kern-Schale-Strukturen oder Janus-Partikel zu erzeugen. Diese Arbeiten fuhrten zu zahlreichen Anwendungen beim Transport und bei der kontrollierten Freisetzung von Wirkstoffen, in der Nanoelektronik sowie fur Sensoren, Nahrungserganzungsmittel und Kosmetika.

The generation of novel multifunctional materials with hierarchical ordering is a major focus of current materials science and engineering. For such endeavors, fluid interfaces, such as air-liquid and liquid-liquid interfaces, offer ideal platforms where nanoparticles or colloidal particles can accumulate and self-assemble. Different assembly processes and reactions have been performed at fluid interfaces to generate hierarchical structures, including two-dimensional crystalline films, colloidosomes, raspberry-like core-shell structures, and Janus particles, which lead to broad applications in drug delivery and controlled release, nanoelectronics, sensors, food supplements, and cosmetics.

Dynamic self-assembly of nonvolatile solutes via controlled solvent evaporation has been exploited as a simple route to create a variety of hierarchically assembled structures. In this work, two glass slides were used to form a confined space in which a solution of a rodlike nanoparticle, tobacco mosaic virus (TMV), was evaporated to create large-scale stripe patterns. The height and width of the stripes are dependent on the TMV concentration. The large-scale-patterned surfaces can be applied to control surface hydrophobicity and direct the growth of bone marrow stromal cells. We systematically studied the effects of stripe width and height on surface hydrophobicity using optical microscopy, atomic force microscopy, and contact angle measurements. This technique offers a facile approach to form 2D patterns on a large surface from a wide range of proteins as well as other biomacromolecules.

By means of a slow drying process and the control of surface charge characteristics, protein stripe patterns were readily prepared on the luminal surface of a capillary. We systematically studied the effects of surface properties, pH, and protein concentration on pattern formation using optical microscopy, atomic force microscopy, and quartz crystal microbalance measurement. By balancing these parameters, a broad selection of proteins could be assembled within a capillary with well-defined stripe patterns. Neutravidin, one of the model proteins, was specifically chosen to demonstrate the bioactivity retained through the assembly process by interaction with fluorescently labeled biotin motifs. This technique therefore offers a facile approach for patterning proteins and other biomacromolecules in capillary tubes.