Charge Balancing of Model Gold-Nanoparticle-Peptide Conjugates Controlled by the Peptide’s Net Charge and the Ligand to Nanoparticle Ratio

As one of the main influenza antigens, neuraminidase (NA) in H3N2 virus has evolved extensively for more than 50 years due to continuous immune pressure. While NA has recently emerged as an effective vaccine target, biophysical constraints on the antigenic evolution of NA remain largely elusive. Here, we apply combinatorial mutagenesis and next-generation sequencing to characterize the local fitness landscape in an antigenic region of NA in six different human H3N2 strains that were isolated around 10 years apart. The local fitness landscape correlates well among strains and the pairwise epistasis is highly conserved. Our analysis further demonstrates that local net charge governs the pairwise epistasis in this antigenic region. In addition, we show that residue coevolution in this antigenic region is correlated with the pairwise epistasis between charge states. Overall, this study demonstrates the importance of quantifying epistasis and the underlying biophysical constraint for building a model of influenza evolution.

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Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing

10.1101/2021.07.10.451918 ◽

2021 ◽

Author(s):

Yiquan Wang ◽

Ruipeng Lei ◽

Armita Nourmohammad ◽

Nicholas C. Wu

Keyword(s):

Fitness Landscape ◽

H3n2 Virus ◽

Effective Vaccine ◽

Human Influenza ◽

Net Charge ◽

Antigenic Region ◽

Immune Pressure ◽

Antigenic Evolution ◽

Charge Balancing ◽

Influenza H3n2

As one of the main influenza antigens, neuraminidase (NA) in H3N2 virus has evolved extensively for more than 50 years due to continuous immune pressure. While NA has emerged as an effective vaccine target recently, biophysical constraints on the antigenic evolution of NA remain largely elusive. Here, we apply deep mutational scanning to characterize the local fitness landscape in an antigenic region of NA in six different human H3N2 strains that were isolated around 10 years apart. The local fitness landscape correlates well among strains and the pairwise epistasis is highly conserved. Our analysis further demonstrates that local net charge governs the pairwise epistasis in this antigenic region. In addition, we show that residue coevolution in this antigenic region can be predicted by charge states and pairwise epistasis. Overall, this study demonstrates the importance of quantifying epistasis and the underlying biophysical constraint for building a predictive model of influenza evolution.

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Adjusting the Metrics of 1-D Helical Gold Nanoparticle Superstructures Using Multivalent Peptide Conjugates

Langmuir ◽

10.1021/acs.langmuir.5b02208 ◽

2015 ◽

Vol 31 (34) ◽

pp. 9492-9501 ◽

Cited By ~ 22

Author(s):

Andrea D. Merg ◽

Joseph Slocik ◽

Martin G. Blaber ◽

George C. Schatz ◽

Rajesh Naik ◽

...

Keyword(s):

Gold Nanoparticle ◽

Peptide Conjugates

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Multivalent gold nanoparticle–peptide conjugates for targeting intracellular bacterial infections

Nanoscale ◽

10.1039/c7nr04062h ◽

2017 ◽

Vol 9 (37) ◽

pp. 14074-14093 ◽

Cited By ~ 26

Author(s):

Rimi Chowdhury ◽

Humaira Ilyas ◽

Anirban Ghosh ◽

Haydar Ali ◽

Arup Ghorai ◽

...

Keyword(s):

Animal Model ◽

Antimicrobial Peptide ◽

Gold Nanoparticle ◽

Bacterial Infections ◽

Intracellular Bacteria ◽

Nano Particle ◽

Peptide Conjugates

This study identifies and characterizes a gold nano-particle tagged antimicrobial peptide that can internalize cells and kill intracellular bacteria without being cytotoxic. It can also considerably reduceS.Typhi infection in animal model.

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Characteristics of an Electrostatic Phase Plate

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100096345 ◽

1972 ◽

Vol 30 ◽

pp. 618-619

Author(s):

William Krakow ◽

Benjamin Siegel

Keyword(s):

Phase Contrast ◽

Objective Lens ◽

Phase Plate ◽

Net Charge ◽

Phase Plates ◽

Beam Currents ◽

Contrast Image ◽

Bright Phase ◽

Additional Phase Shift ◽

Additional Phase

Unwin has used a metallized non-conducting thread in the back focal plane of the objective lens that stops out a portion of the unscattered beam, takes on a localized positive charge and thus produces an additional phase shift to give a different transfer function of the lens. Under the particular conditions Unwin used, the phase contrast image was shifted to bright phase contrast for optimum focus.We have investigated the characteristics of this type of electrostatic phase plate, both analytically and experimentally, as functions of the magnitude of charge and defocus. Phase plates have been constructed by using Wollaston wire to mount 0.25μ diameter platinum wires across apertures ranging from 50 to 200μ diameter and vapor depositing SiO and gold on the mounted wires to give them the desired charging characteristics. The net charge was varied by adjusting only the bias on the Wehnelt shield of the gun, and hence the beam currents and effective size of the source.

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Direct imaging of charge transfer

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100165860 ◽

1996 ◽

Vol 54 ◽

pp. 680-681

Author(s):

Yimei Zhu ◽

J. Tafto

Keyword(s):

Charge Transfer ◽

Electron Diffraction ◽

Scattering Amplitude ◽

High Temperature Superconductors ◽

Charge Carriers ◽

Image Charge ◽

Net Charge ◽

Long Time ◽

Electron Holes ◽

First Time

The electron holes confined to the CuO2-plane are the charge carriers in high-temperature superconductors, and thus, the distribution of charge plays a key role in determining their superconducting properties. While it has been known for a long time that in principle, electron diffraction at low angles is very sensitive to charge transfer, we, for the first time, show that under a proper TEM imaging condition, it is possible to directly image charge in crystals with a large unit cell. We apply this new way of studying charge distribution to the technologically important Bi2Sr2Ca1Cu2O8+δ superconductors.Charged particles interact with the electrostatic potential, and thus, for small scattering angles, the incident particle sees a nuclei that is screened by the electron cloud. Hence, the scattering amplitude mainly is determined by the net charge of the ion. Comparing with the high Z neutral Bi atom, we note that the scattering amplitude of the hole or an electron is larger at small scattering angles. This is in stark contrast to the displacements which contribute negligibly to the electron diffraction pattern at small angles because of the short g-vectors.

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Separation of Heparin into Subtractions by DEAE-Cellulose Chromatography

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657046 ◽

1979 ◽

Vol 42 (05) ◽

pp. 1452-1459 ◽

Cited By ~ 4

Author(s):

Robert H Yue ◽

Toby Starr ◽

Menard M Gertler

Keyword(s):

High Activity ◽

Uronic Acid ◽

Deae Cellulose ◽

Exchange Chromatography ◽

Net Charge ◽

Uronic Acid Content ◽

Successful Separation ◽

Salt Gradient ◽

Structure And Activity ◽

Low Activity

SummaryCommercial porcine heparin can be separated into three distinct subtractions by using DEAE-cellulose chromatography and a stepped salt gradient. Gram quantities of heparin can be fractionated by this technique. All three heparin subtractions can accelerate the inhibition of thrombin by antithrombin III with different efficiency. The specific activities of the high activity heparin, intermediate activity heparin and low activity heparin are 228 units/mg, 142 units/mg and 95 units/mg, respectively. Both the uronic acid content and the quantity of N-SO4 for all three heparin subfractions have been evaluated. The high activity heparin has the lowest uronic acid and N-SO4 content. The successful separation of commercial heparin into three distinct subfractions by means of ion-exchange chromatography suggests that the net charge on these three heparin components will serve as a model system in the elucidation of the structure and activity relationship to the biological function of heparin.

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