RESUMO
Multiple studies have demonstrated that various nanoparticles (NPs) stimulate osteogenic differentiation of mesenchymal stem cells (MSCs) and inhibit adipogenic ones. The mechanisms of these effects are not determined. The aim of this paper was to estimate Wharton's Jelly MSCs phenotype and humoral factor production during tri-lineage differentiation per se and in the presence of silicon-gold NPs. Silicon (SiNPs), gold (AuNPs), and 10% Au-doped Si nanoparticles (SiAuNPs) were synthesized by laser ablation, characterized, and studied in MSC cultures before and during differentiation. Humoral factor production (n = 41) was analyzed by Luminex technology. NPs were nontoxic, did not induce ROS production, and stimulated G-CSF, GM-CSF, VEGF, CXCL1 (GRO) production in four day MSC cultures. During MSC differentiation, all NPs stimulated CD13 and CD90 expression in osteogenic cultures. MSC differentiation resulted in a decrease in multiple humoral factor production to day 14 of incubation. NPs did not significantly affect the production in chondrogenic cultures and stimulated it in both osteogenic and adipogenic ones. The major difference in the protein production between osteogenic and adipogenic MSC cultures in the presence of NPs was VEGF level, which was unaffected in osteogenic cells and 4-9 times increased in adipogenic ones. The effects of NPs decreased in a row AuNPs > SiAuNPs > SiNPs. Taken collectively, high expression of CD13 and CD90 by MSCs and critical level of VEGF production can, at least, partially explain the stimulatory effect of NPs on MSC osteogenic differentiation.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Ouro/farmacologia , Nanopartículas Metálicas/administração & dosagem , Secretoma/efeitos dos fármacos , Silício/farmacologia , Geleia de Wharton/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Animais , Antígenos CD13/metabolismo , Condrogênese/efeitos dos fármacos , Feminino , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Fenótipo , Secretoma/metabolismo , Antígenos Thy-1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Geleia de Wharton/metabolismoRESUMO
A series of new fluorescent symmetric dimeric bisbenzimidazoles DBP(n) bearing bisbenzimidazole fragments joined by oligomethylene linkers with a central 1,4-piperazine residue were synthesized. The complex formation of DBP(n) in the DNA minor groove was demonstrated. The DBP(n) at micromolar concentrations inhibit in vitro eukaryotic DNA topoisomerase I and prokaryotic DNA methyltransferase (MTase) M.SssI. The DBP(n) were soluble well in aqueous solutions and could penetrate cell and nuclear membranes and stain DNA in live cells. The DBP(n) displayed a moderate effect on the reactivation of gene expression.
Assuntos
Bisbenzimidazol/análogos & derivados , DNA/química , DNA/efeitos dos fármacos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Bisbenzimidazol/síntese química , Bisbenzimidazol/farmacologia , Linhagem Celular , DNA/genética , DNA-Citosina Metilases/antagonistas & inibidores , Dimerização , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Corantes Fluorescentes/química , Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Camundongos , Microscopia de Fluorescência , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/farmacologiaRESUMO
Maxillofacial defects, arising from trauma, oncological disease or congenital abnormalities, detrimentally affect daily life. Prosthetic repair offers the aesthetic and functional reconstruction with the help of materials mimicking natural tissues. 3D polymer printing enables the design of patient-specific prostheses with high structural complexity, as well as rapid and low-cost fabrication on-demand. However, 3D printing for prosthetics is still in the early stage of development and faces various challenges for widespread use. This is because the most suitable polymers for maxillofacial restoration are soft materials that do not have the required printability, mechanical strength of the printed parts, as well as functionality. This review focuses on the challenges and opportunities of 3D printing techniques for production of polymer maxillofacial prostheses using computer-aided design and modeling software. Review discusses the widely used polymers, as well as their blends and composites, which meet the most important assessment criteria, such as the physicochemical, biological, aesthetic properties and processability in 3D printing. In addition, strategies for improving the polymer properties, such as their printability, mechanical strength, and their ability to print multimaterial and architectural structures are highlighted. The current state of the prosthetic retention system is presented with a focus on actively used polymer adhesives and the recently implemented prosthesis-supporting osseointegrated implants, with an emphasis on their creation from 3D-printed polymers. The successful prosthetics is discussed in terms of the specificity of polymer materials at the restoration site. The approaches and technological prospects are also explored through the examples of the nasal, auricle and ocular prostheses, ranging from prototypes to end-use products.
Assuntos
Prótese Maxilofacial , Polímeros , Impressão Tridimensional , Humanos , Polímeros/química , Desenho de Prótese , Desenho Assistido por Computador , Animais , Retenção da Prótese/métodosRESUMO
It is generally accepted that oxidative stress plays a key role in the development of ischemia-reperfusion injury in ischemic heart disease. However, the mechanisms how reactive oxygen species trigger cellular damage are not fully understood. Our study investigates redox state and highly reactive substances within neonatal and adult cardiomyocytes under hypoxia conditions. We have found that hypoxia induced an increase in H2O2 production in adult cardiomyocytes, while neonatal cardiomyocytes experienced a decrease in H2O2 levels. This finding correlates with our observation of the difference between the electron transport chain (ETC) properties and mitochondria amount in adult and neonatal cells. We demonstrated that in adult cardiomyocytes hypoxia caused the significant increase in the ETC loading with electrons compared to normoxia. On the contrary, in neonatal cardiomyocytes ETC loading with electrons was similar under both normoxic and hypoxic conditions that could be due to ETC non-functional state and the absence of the electrons transfer to O2 under normoxia. In addition to the variations in H2O2 production, we also noted consistent pH dynamics under hypoxic conditions. Notably, the pH levels exhibited a similar decrease in both cell types, thus, acidosis is a more universal cellular response to hypoxia. We also demonstrated that the amount of mitochondria and the levels of cardiac isoforms of troponin I, troponin T, myoglobin and GAPDH were significantly higher in adult cardiomyocytes compared to neonatal ones. Remarkably, we found out that under hypoxia, the levels of cardiac isoforms of troponin T, myoglobin, and GAPDH were elevated in adult cardiomyocytes, while their level in neonatal cells remained unchanged. Obtained data contribute to the understanding of the mechanisms of neonatal cardiomyocytes' resistance to hypoxia and the ability to maintain the metabolic homeostasis in contrast to adult ones.
Assuntos
Peróxido de Hidrogênio , Miócitos Cardíacos , Ratos , Animais , Miócitos Cardíacos/metabolismo , Peróxido de Hidrogênio/metabolismo , Mioglobina , Troponina T/metabolismo , Hipóxia Celular , Hipóxia/metabolismo , Oxirredução , Isoformas de Proteínas/metabolismoRESUMO
The lack of oxygen (O2) causes changes in the cell functioning. Modeling hypoxic conditions in vitro is challenging given that different cell types exhibit different sensitivities to tissue O2 levels. We present an effective in vivo platform for assessing various tissue and organ parameters in Danio rerio larvae under acute hypoxic conditions. Our system allows simultaneous positioning of multiple individuals within a chamber where O2 level in the water can be precisely and promptly regulated, all while conducting microscopy. We applied this approach in combination with a genetically encoded pH-biosensor SypHer3s and a highly H2O2-sensitive Hyper7 biosensor. Hypoxia causes H2O2 production in areas of brain, heart and skeletal muscles, exclusively in the mitochondrial matrix; it is noteworthy that H2O2 does not penetrate into the cytosol and is neutralized in the matrix upon reoxygenation. Hypoxia causes pronounced tissue acidosis, expressed by a decrease in pH by 0.4-0.6 units everywhere. Using imaging photoplethysmography, we measured in D.rerio fry real-time heart rate decrease under conditions of hypoxia and subsequent reoxygenation. Our observations in this experimental system lead to the hypothesis that mitochondria are the only source of H2O2 in cells of D.rerio under hypoxia.
RESUMO
Semiconductor quantum dots (QDs) are proved to be unique fluorescent labels providing excellent possibilities for high-throughput detection and diagnostics. To explore in full QDs' advantages in brightness, photostability, large Stokes shift, and tunability by size fluorescence emission, they should be rendered stable in biological fluids and tagged with the target-specific capture molecules. Ideal QD-based nanoprobes should not exceed 15nm in diameter and should contain on their surface multiple copies of homogeneously oriented highly active affinity molecules, for example, antibodies (Abs). Direct conjugation of QDs with the Abs through cross-linking of QDs' amines with the sulfhydryl groups issued from the reduced Abs' disulfide bonds is the common technique. However, this procedure often generates conjugates in which the number of functionally active Abs on the surface of QDs does not always conform to expectations and is often low. Here we have developed an advanced procedure with the optimized critical steps of Ab reduction, affinity purification, and QD-Ab conjugation. We succeeded in reducing the Abs in such a way that the reduction reaction yields highly functional, partially cleaved, 75-kDa heavy-light Ab fragments. Affinity purification of these Ab fragments followed by their tagging with the QDs generates QD-Ab conjugates with largely improved functionality compared with those produced according to the standard procedures. The developed approach can be extended to conjugation of any type of Ab with different semiconductor, noble metal, or magnetic nanocrystals.
Assuntos
Anticorpos/química , Imunoensaio/métodos , Pontos Quânticos , Anticorpos/imunologia , Antígenos CD4/análise , Antígenos CD4/imunologia , Dissulfetos/química , Corantes Fluorescentes/química , Humanos , Oxirredução , Semicondutores , Espectrometria de Fluorescência/métodosRESUMO
Low-frequency hysteresis loops and specific absorption rate (SAR) of various assemblies of elongated spheroidal magnetite nanoparticles have been calculated for a range of particle semiaxis ratios a/b = 1.0-3.0. The SAR of a dilute randomly oriented assembly of magnetite nanoparticles in an alternating magnetic field of moderate frequency, f = 300 kHz, and amplitude H 0 = 100-200 Oe is shown to decrease significantly with an increase in the aspect ratio of nanoparticles. In addition, there is a narrowing and shift of the intervals of optimal particle diameters towards smaller particle sizes. However, the orientation of a dilute assembly of elongated nanoparticles in a magnetic field leads to an almost twofold increase in SAR at the same frequency and amplitude of the alternating magnetic field, the range of optimal particle diameters remaining unchanged. The effect of the magneto-dipole interaction on the SAR of a dilute assembly of oriented clusters of elongated magnetite nanoparticles has also been investigated depending on the volume fraction of nanoparticles in a cluster. It has been found that the SAR of the assembly of oriented clusters decreases by approximately an order of magnitude with an increase in the volume fraction of nanoparticles in a cluster in the range of 0.04-0.2.
RESUMO
One-dimensional (1D) necklace-like assembly of inorganic nanoparticles exhibits unique collective properties, which are critical to open up new and remarkable opportunities in the field of nanotechnology. This review focuses on the recent advances in the production of these types of assemblies employing two strategies: colloidal synthesis and self-assembly procedures. After a brief description of the forces guiding nanoparticles towards the assembly, the main features of both strategies are discussed. Examples of approaches, typically involved in colloidal synthesis, are highlighted. The peculiar properties of 1D nanostructures are strictly associated with the nanoparticle arrangement in the form of highly ordered assemblies, which are attained during the synthesis both in the solution and using a template, as well as under the action of an external force. The various 1D necklace-like structures, created through nanoparticle self-assembly, demonstrate aligned, oriented nanoparticle organization. Diverse nature, size and shape of preformed particles as building blocks, along with utilizing different linkers, templates or external field lead to fabrication of 1D chain nanostructures with properties responsible for their wide applications. The unique structure-property relationship, both in colloidal synthesis, and self-assembly, offers broad spectrum of 1D necklace-like nanostructure implementations, illustrated by their use in photonics, electronics, electrocatalysis, magnetics.
RESUMO
To the present, different efficient but expensive, multistage, and time-consuming technologies have been developed to deliver ribonucleic acids (RNA) into eukaryotic cells. Here, we report a simple and feasible solution to design RNA nanocarriers based on nucleic acid condensation by bi- and trivalent metal ions during thermal cycling. Efficient RNA conversion to nanoparticles with small size (10-50 nm) suitable for transfection was achieved using cations Ni2+, Co2+ or Cu2+ alone or in combination with Ca2+ at the specially selected concentrations (2.0 mM-3.5 mM), low ionic strength, and narrow pH range (8.0-8.5). Other ions - Mn2+, Zn2+, Tb3+, or Gd3+ - caused RNA-cleaving effect that was abolished in the presence of Ni2+, Co2+, Zn2+, or Cu2+. Naked RNA-metal ion nanoparticles were extremely unstable in phosphate buffer and sensitive to serum ribonucleases (RNases), and this problem was solved by treatment with polyarginines-16 and 8. Polyarginine-stabilized nanoparticles, containing malachite green (MG) aptamer RNA and metal cations, crossed the cell membrane, dissociated in the cytoplasm, and preserved the functionality of transported RNA, as judged from efficient transfection of human embryonic kidney 293 cells. The technology, involving RNA condensation by metal cations, can be used as a cheap alternative to produce nanoscale carriers to deliver various RNAs into cells in vitro and in vivo.Communicated by Ramaswamy H. Sarma.
Assuntos
Nanopartículas , RNA , Cátions , Humanos , Metais , TransfecçãoRESUMO
Interaction between porphyrins and quantum dots (QD) via energy and/or charge transfer is usually accompanied by reduction of the QD luminescence intensity and lifetime. However, for CdSe/ZnS-Cys QD water solutions, kept at 276 K during 3 months (aged QD), the significant increase in the luminescence intensity at the addition of meso-tetrakis (p-sulfonato-phenyl) porphyrin (TPPS4) has been observed in this study. Aggregation of QD during the storage provokes reduction in the quantum yield and lifetime of their luminescence. Using steady-state and time-resolved fluorescence techniques, we demonstrated that TPPS4 stimulated disaggregation of aged CdSe/ZnS-Cys QD in aqueous solutions, increasing the quantum yield of their luminescence, which finally reached that of the fresh-prepared QD. Disaggregation takes place due to increase in electrostatic repulsion between QD at their binding with negatively charged porphyrin molecules. Binding of just four porphyrin molecules per single QD was sufficient for total QD disaggregation. The analysis of QD luminescence decay curves demonstrated that disaggregation stronger affected the luminescence related with the electron-hole annihilation in the QD shell. The obtained results demonstrate the way to repair aged QD by adding of some molecules or ions to the solutions, stimulating QD disaggregation and restoring their luminescence characteristics, which could be important for QD biomedical applications, such as bioimaging and fluorescence diagnostics. On the other hand, the disaggregation is important for QD applications in biology and medicine since it reduces the size of the particles facilitating their internalization into living cells across the cell membrane.
RESUMO
In the past decade correlative microscopy, which combines the potentials of different types of high-resolution microscopies with a variety of optical microspectroscopy techniques, has been attracting increasing attention in material science and biological research. One of outstanding solutions in this area is the combination of scanning probe microscopy (SPM), which provides data on not only the topography, but also the spatial distribution of a wide range of physical properties (elasticity, conductivity, etc.), with ultramicrotomy, allowing 3D multiparametric examination of materials. The combination of SPM and ultramicrotomy (scanning probe nanotomography) is very appropriate for characterization of soft multicompound nanostructurized materials, such as polymer matrices and microstructures doped with different types of nanoparticles (magnetic nanoparticles, quantum dots, nanotubes, etc.), and biological materials. A serious problem of this technique is a lack of chemical and optical characterization tools, which may be solved by using optical microspectroscopy. Here, we report the development of an instrumental approach to combining confocal microspectroscopy and 3D scanning probe nanotomography in a single apparatus. This approach retains all the advantages of SPM and upright optical microspectroscopy and allows 3D multiparametric characterization using both techniques. As the first test of the system developed, we have performed correlative characterization of the morphology and the magnetic and fluorescent properties of fluorescent magnetic microspheres doped with a fluorescent dye and magnetic nanoparticles. The results of this study can be used to obtain 3D volume images of a specimen for most high-resolution near-field scanning probe microscopies: SNOM, TERS, AFM-IR, etc. This approach will result in development of unique techniques combining the advantages of SPM (nanoscale morphology and a wide range of physical parameters) and high-resolution optical microspectroscopy (nanoscale chemical mapping and optical properties) and allowing simultaneous 3D measurements.
RESUMO
We present a new concept of a combined scanning probe microscope (SPM)/ultramicrotome apparatus. It enables "slice-and-view" scanning probe nanotomography measurements and 3D reconstruction of the bulk sample nanostructure from series of SPM images after consecutive ultrathin sections. The sample is fixed on a flat XYZ scanning piezostage mounted on the ultramicrotome arm. The SPM measuring head with a cantilever tip and a laser-photodiode tip detection system approaches the sample for SPM measurements of the block-face surface immediately after the ultramicrotome sectioning is performed. The SPM head is moved along guides that are also fixed on the ultramicrotome arm. Thereby, relative dysfunctional displacements of the tip, the sample, and the ultramicrotome knife are minimized. The design of the SPM head enables open frontal optical access to the sample block-face adapted for high-resolution optical lenses for correlative SPM/optical microscopy applications. The new system can be used in a wide range of applications for the study of 3D nanostructures of biological objects, biomaterials, polymer nanocomposites, and nanohybrid materials in various SPM and optical microscopy measuring modes.
RESUMO
Behavior of P-glycoprotein (Pgp) natural lipid environment within the membrane of CEM cells expressing Pgp in the quantities varying from 0% to 32% of the total amount of all membrane proteins is described for the first time. Observed cooperative effect of Pgp-induced increase of membrane stability, decrease of the temperature of gel-to-crystal lipids transition and predominance of the lipid liquid crystalline phase at physiological temperatures should have an impact in development of multidrug resistance phenotype of tumor cells by favoring the Pgp intercellular transfer and Pgp ATPase activity.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Lipídeos/química , Microdomínios da Membrana/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Humanos , Microdomínios da Membrana/metabolismo , Análise Espectral Raman , Propriedades de Superfície , TemperaturaRESUMO
The development of bio-sensitized nanofilms engineered from biomembrane components and inorganic nanoparticles is a promising field of colloid and interface science and technologies. Recent nano-bioengineering approaches employing quantum dots (QDs) permit the enhancement of the purple membrane (PM) "light-harvesting capacity" compared to native PMs. The influence of QDs on the PM properties, especially the bacteriorhodopsin (bR) photocycle, has been found that has both fundamental (mechanisms of photoreception) and applied implications (including the fabrication of hybrid bionanomaterials). Samples of PM-QD complexes capable of energy transfer and characterized by increased rates of M-intermediate formation and decay have been obtained. The modified bR photocycle kinetic parameters may be explained by changes in the PM interface upon QD adsorption. The increase and decrease in absorption at 410 nm (or photopotential) for PM-QD complexes are, on average, several times more rapid than for PM suspensions or PM dry films. These results provide a strong impetus for the development of nanomaterials with advanced properties.
Assuntos
Membrana Purpúrea/química , Pontos Quânticos/química , Transferência Ressonante de Energia de Fluorescência , Halobacterium salinarum/química , CinéticaRESUMO
Composite polymer particles consisting of a solid poly(acrolein-co-styrene) core and a poly(N-vinylcaprolactam) (PVCL) polymer shell doped with CdSe/ZnS semiconductor quantum dots (QDs) were fabricated. The temperature response of the composite particles was observed as a decrease in their hydrodynamic diameter upon heating above the lower critical solution temperature of the thermosensitive PVCL polymer. Embedding QDs in the PVCL shell yields particles whose fluorescence is sensitive to temperature changes. This sensitivity was determined by the dependence of the QD fluorescence intensity on the distances between them in the PVCL shell, which reversibly change as a result of the temperature-driven conformational changes in the polymer. The QD-containing thermosensitive particles were assembled with protein molecules in such a way that they retained their thermosensitive properties, including the completely reversible temperature dependence of their fluorescence response. The composite particles developed can be used as local temperature sensors, as carriers for biomolecules, as well as in biosensing and various bioassays employing optical detection schemes.
Assuntos
Acroleína/química , Compostos de Cádmio/química , Caprolactama/análogos & derivados , Polímeros/química , Poliestirenos/química , Pontos Quânticos , Compostos de Selênio/química , Sulfetos/química , Compostos de Zinco/química , Caprolactama/química , Fluorescência , Corantes Fluorescentes/química , Hidrodinâmica , TemperaturaRESUMO
Optical sensing polymer particles with tailored semiconductor nanocrystal (QD) loading are prepared by layer-by-layer deposition technique (LbL). Polyacrolein particles of 1.2 µm diameter are used as solid support for deposition of hydrophilic CdSe/ZnS nanocrystal/polyelectrolyte multilayers formed by electrostatic interactions. The pH-dependent fluorescence of QDs and pH-dependent conformations of polyelectrolytes, which likely passivate the surface state of nanocrystals, allow a creation of both mono- and multiplex coded polymer particles with pH-dependent fluorescence intensity. Bovine serum albumin (BSA) as outermost layer makes it possible to design the optical sensing polymer particles with reversibly responded fluorescence at pH variations. The fluorescence of such polymer particles with BSA outer layer is sensitive to copper(II) ion while the fluorescence of these particles is practically insensitive to the other divalent cations (Zn(2+), Ca(2+), Ba(2+), Co(2+), Mg(2+)). The detection limit of Cu(2+) is about 15 nM. Adaptation of LbL method to prepare QD-labeled polymer particles with enhanced complexity (e.g. several types of QDs, multiple biofunctionality) is expected to open new opportunities in biotechnological applications.
Assuntos
Acroleína/química , Nanopartículas/química , Polímeros/química , Pontos Quânticos , Soroalbumina Bovina/química , Animais , Bovinos , Concentração de Íons de Hidrogênio , Proteínas Imobilizadas/química , Modelos Biológicos , Espectrometria de Fluorescência , Propriedades de SuperfícieRESUMO
AIM: This study aimed to design a panel of uniform particulate biochemical reagents and to test them in specific bioassays. These reagents are polymer particles of different sizes doped with semiconductor nanocrystals and conjugated with either full-size antibodies or recombinant mini-antibodies (4D5 scFv fragment) designed by genetic engineering approaches. MATERIALS & METHODS: A panel of highly fluorescent polymer particles (150-800 nm) were formed by embedding CdSe/ZnS nanocrystals (quantum dots) into preformed polyacrolein and poly(acrolein-co-styrene) particles. Morphology, content and fluorescence characteristics of the prepared materials were studied by laser correlation spectroscopy, spectrophotometry, optical and fluorescent microscopy and fluorimetry. RESULTS: The obtained fluorescent particles sensitized by anti-Yersinia pestis antibodies were used for rapid agglutination glass test suitable for screening analysis of Y. pestis antigen and for microtiter particle agglutination, which, owing to its speed and simplicity, is very beneficial for diagnostic detection of Y. pestis antigen. Recombinant 4D5 scFv antibodies designed and conjugated with polymer particles containing quantum dots provide multipoint highly specific binding with cancer marker HER2/neu on the surface of SKOV-3 cell.
Assuntos
Compostos de Cádmio/química , Nanopartículas/química , Neoplasias Ovarianas/diagnóstico , Peste/diagnóstico , Compostos de Selênio/química , Sulfetos/química , Yersinia pestis/isolamento & purificação , Compostos de Zinco/química , Acroleína/química , Técnicas Biossensoriais/métodos , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/química , Fluorimunoensaio/métodos , Humanos , Imunoconjugados/química , Nanotecnologia/métodos , Polímeros/química , Semicondutores , Yersinia pestis/imunologiaRESUMO
Tetraantennary peptides [glycine(n)-NHCH(2)](4)C can form stable noncovalent structures by self-assembly through intermolecular hydrogen bonding. The oligopeptide chains assemble as polyglycine II to yield submicron-sized, flat, one-molecule-thick sheets. Attachment of alpha-N-acetylneuraminic acid (Neu5Acalpha) to the terminal glycine residues gives rise to water-soluble assembled glycopeptides that are able to bind influenza virus multivalently and inhibit adhesion of the virus to cells 10(3)-fold more effectively than a monomeric glycoside of Neu5Acalpha. Another antiviral strategy based on virus-promoted assembly of the glycopeptides was also demonstrated. Consequently, the self-assembly principle offers new perspectives on the design of multivalent antivirals.