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Shen L.,Columbia University | Wang Y.,Microsurfaces, Inc. | Lin C.-I.,University of Texas at Austin | Liu H.-W.,University of Texas at Austin | And 2 more authors.
ACS Chemical Biology | Year: 2014

The binding of lectins to glycan receptors on the host cell surface is a key step contributing to the virulence and species specificity of most viruses. This is exemplified by the viral protein hemagglutinin (HA) of the influenza A virus, whose binding specificity is modulated by the linkage pattern of terminal sialic acids on glycan receptors of host epithelial cells. Such specificity dictates whether transmission is confined to a particular animal species or jumps between species. Here, we show, using H5N1 avian influenza as a model, that the specific binding of recombinant HA to α2-3 linked sialic acids can be enhanced dramatically by interaction with the surface of the lipid membrane. This effect can be quantitatively accounted for by a two-stage process in which weak association of HA with the membrane surface precedes more specific and tighter binding to the glycan receptor. The weak protein-membrane interaction discovered here in the model system may play an important secondary role in the infection and pathogenesis of the influenza A virus. © 2014 American Chemical Society.


Shen L.,University of Texas at Austin | Garland A.,University of Texas at Austin | Wang Y.,Microsurfaces, Inc. | Li Z.,University of Texas at Austin | And 3 more authors.
Small | Year: 2012

Protein molecules on solid surfaces are essential to a number of applications, such as biosensors, biomaterials, and drug delivery. In most approaches for protein immobilization, inter-molecular distances on the solid surface are not controlled and this may lead to aggregation and crowding. Here, a simple approach to immobilize individual protein molecules in a well-ordered 2D array is shown, using nanopatterns obtained from a polystyrene-block-poly(2- hydroxyethyl methacrylate) (PS-b-PHEMA) diblock copolymer thin film. This water-stable and protein-resistant polymer film contains hexagonally ordered PS cylindrical domains in a PHEMA matrix. The PS domains are activated by incorporating alkyne-functionalized PS and immobilizing azide-tagged proteins specifically onto each PS domain using "Click" chemistry. The nanometer size of the PS domain dictates that each domain can accommodate no more than one protein molecule, as verified by atomic force microscopy imaging. Immunoassay shows that the amount of specifically bound antibody scales with the number density of individual protein molecules on the 2D nanoarrays. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Shen L.,University of Texas at Austin | Guo A.,Microsurfaces, Inc. | Zhu X.,University of Texas at Austin
Surface Science | Year: 2011

Tween surfactants, each containing hydrophilic ethylene glycol head groups and a hydrophobic alkyl tail, are being actively explored as protein-resistant surface coatings, but little is known about how they adsorb on surfaces. We carry out a comparative study of the adsorption of two Tween molecules (same hydrophilic head group, but a shorter dodecyl tail for Tween 20 and a longer octadecyl tail for Tween 40) on Au and polystyrene surfaces. Despite the similarity between these two molecules, there is a drastic difference in their protein resistance: a monolayer of Tween 20 on a hydrophobic surface is repulsive against protein adsorption but that of Tween 40 is not. The difference in protein resistance can be attributed to two distinctly different adsorption mechanisms. While the adsorption of Tween 40 is described by a simple first-order mechanism, that of Tween 20 consists of a fast adsorption step and a slower reorganization process at a high surface coverage. The latter leads to the formation of a high-density and self-organized monolayer, which is responsible for the enhanced stability and resistance against non-specific protein adsorption. © 2010 Elsevier B.V. All rights reserved.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 746.99K | Year: 2011

DESCRIPTION (provided by applicant): This research project aims to develop fluidic glycan microarrays for the quantitative profiling and characterization of pathogens, and for the screening of pathogen inhibitors and the development of vaccines. The approach targets a common mechanism at the initial stage of pathogen attack: the recognition of and attachment onto host cells via multivalent interaction between receptor proteins and glycan molecules. The tremendous variation in glycans and the complexity inmultivalent interaction have necessitated the use of large-scale profiling and analysis techniques, particularly glycan microarrays. The proposed fluidic approach overcomes two major limitations of current glycan microarray technology: the lack of mobilityand the difficulty in quantitatively controlling glycan density. Multivalent cell surface interactions often require mobility of the fluidic cell membrane environment and are strong functions of surface glycan density. In order to quantitatively apply theglycan microarray in profiling and characterization, one must ensure mobility and control of glycan density over a broad range. The specific aims during phase-II are: Aim 1: using haemagglutinin, a predominant antigen on influenza viruses, and the dendritic cell receptor DC-SIGN, a binding receptor for mannose moieties on HIV-1 virus, as model systems and establish the roles of secondary interactions in binding affinity, avidity, and specificity. These experiments will establish the general applicability of the fluidic microarrays in profiling and characterizing complex pathogen-cell surface interactions; Aim 2: using several strains of E. coli with varying affinity and selectivity towards mannose as model systems and establishing that the fluidic and density gradient glycan microarray can be used to quantitatively profile the variability in binding affinity and multivalency among strains of the same species. Quantifying such variability is essential to the understanding and surveillance of how random mutations can lead to new pathogen threats, as exemplified by the recent outbreaks of avian flu and swine flu; Aim 3: To establish chemical procedures for the optimization of the fluidic glycan microarray, including spatial confinement of the supported lipid bilayer spots, efficient blocking of surfaces outside the spotted areas, recoverability in drying and rehydration of the microarrays, and long term stability of content glycan microarrays. These practical issues must be addressed in developing the fluidic glycan microarray as a viable product. The long-term goal of this RandD plan is to develop an effective high-throughput tool in the combat against pathogen threats. PUBLIC HEALTH RELEVANCE: This research project aims to develop cell-membrane mimickingmicroarrays of sugar molecules for the profiling and characterization of pathogens, and for the screening of vaccines and inhibitors against pathogens. )


Trademark
Microsurfaces, Inc. | Date: 2011-06-14

Protein arrays and nucleotide arrays for scientific and medical research.


Microsurfaces, Inc. | Entity website

Anti-stiction and Anti-Drift coatings for MEMS MSI's MEMS coatings are designed to provide the following characteristics: covalently bonded monolayer, low surface energy, low friction coefficient, thermally and mechanically stable. While they mainly serve as anti-stiction coatings, these monolayers also provide long term surface stability, thus eliminating surface related drifting of device performance ...


Microsurfaces, Inc. | Entity website

Surface Coatings Solve Drift Problems in MEMS [Home | Technology | Stiction] One of the barriers to full commercialization of complex microsystems is reliability. Among a number of process related issues, the difficulty in controlling surface forces is a critical impediment to the fabrication and operation of MEMS devices ...


Microsurfaces, Inc. | Entity website

Anti-Stiction Coatings in MEMS Devices There have been many exciting predictions that the future of micromachines or microelectromechanical systems (MEMS) is just "around the corner", but this future has proven to be slow in coming. Despite the demonstration of numerous MEMS devices and product concepts each year, a very small number have actually succeeded in the market place ...


Microsurfaces, Inc. | Entity website

MicroSurfaces Inc. MicroSurfaces Inc ...


Products & Services from MicroSurfaces, Inc. The ZeroBkg line of surfaces each consisting of a high density brush of poly (ethyleneglycol) (PEG) for extremely low background and chemical functionality for the specific immobilization of proteins, peptides, antibodies and other biomolecules ...

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