The bonding interaction amongst Influenza A and the peptide “PeB,” which selectively binds the viral surface protein hemagglutinin, has been investigated using electrically controlled deoxyribonuclic acid (DNA) nanolevers in the journal Advanced Materials.
PeB is conjugated to DNA strands that are bonded to complementary anchors and fixed on the electrode surface of a “switchSENSE” biochip. A fluorophore is attached to the surface-tethered DNA strand, whereas the complementary strand has a multivalent configuration containing up to three PeB peptides. A negative voltage is used to keep the nanolevers erect (static).
As the current epidemic of the SARS-CoV-2 virus has demonstrated, viral pandemics represent a tremendous threat to humanity. A similar pandemic, known as the Spanish flu, was induced by an influenza A virus and led to millions of fatalities around the world. Annual outbreaks of different intensity are still caused by influenza A viruses. The globe was recently confronted with the swine flu in 2009.
Influenza A is an Orthomyxoviridae virus that is encased in a lipid bilayer that contains three cell membranes: hemagglutinin (HA), neuraminidase (NA), and the M2 proton channels. Neuraminidase is a glycoside cleaver that is essential for the discharge of viral particles from infected cells.
Subsequent to viral fusing, hemagglutinin binds to the host cell’s sialic acid (SA)-containing cellular receptors. Understanding viral internalization and infection requires kinetic analysis of affinity and fervency coefficients of various receptor binding to hemagglutinin.
a) Top view of a switchSENSE microfluidic biochip with four flow channels. Each channel comprises six gold electrodes. The more detailed view shows the six independent measurement electrodes in a row within the microfluidic channel. b) Schematic overview of a single stranded DNA nanolever (NL-B48) immobilized on a gold electrode via thiol coupling. The nanolever carries a fluorophore at the lateral end. c) The DNA monolayer is functionalized with the ligand of interest by hybridization of the complementary DNA strand carrying a receptor molecule at the distal end. d) Dynamic measurement mode: The double stranded DNA nanolever is actuated to a switching motion by applying an alternating potential. The fluorescence signal is gradually quenched by energy transfer upon approaching the gold surface. Read-out of this mode is the switching speed of DNA nanolevers. The switching speed is slowed down upon binding of an analyte to the ligand molecule adding friction to the nanolever. e) Static measurement mode: DNA nanolevers are kept at an upright position. Read-out of this mode is the change in fluorescence intensity upon binding of an analyte due to changes in the local environment of the dye. Drawings are not to scale. Image Credit: Kruse M et al., Advanced Material
The ability to calculate not just the dissociation constant but also rate constants is one of the key features of the switchSENSE technique. These kinetic metrics are becoming increasingly important in determining the effectiveness of candidates in medication development.
Other methods for determining dissociation constants exist, but they lack the capacity to resolve bonding kinetic parameters. Radioligand binding tests, microscale thermophoresis (MST), and isothermal calorimetry are some examples of these.
Surface plasmon resonance is one technology that allows for real-time monitoring of kinetic parameters (SPR). SPR measures and switchSENSE technologies are similar in that they both have benefits and drawbacks. As a result, a similar naming system is used.
The quantifiable metrics of kinetic parameters in a timely manner, label-free detection, minimal sample expenditure, and high sensitivity of the technology are all benefits of SPR and switchSENSE. The disadvantages of both procedures are that one of the participants must be immobilized, which may have an impact on binding behavior, and that mass transfer is limited….
News
Scientists Melt Cancer’s Hidden “Power Hubs” and Stop Tumor Growth
Researchers discovered that in a rare kidney cancer, RNA builds droplet-like hubs that act as growth control centers inside tumor cells. By engineering a molecular switch to dissolve these hubs, they were able to halt cancer [...]
Platelet-inspired nanoparticles could improve treatment of inflammatory diseases
Scientists have developed platelet-inspired nanoparticles that deliver anti-inflammatory drugs directly to brain-computer interface implants, doubling their effectiveness. Scientists have found a way to improve the performance of brain-computer interface (BCI) electrodes by delivering anti-inflammatory drugs directly [...]
After 150 years, a new chapter in cancer therapy is finally beginning
For decades, researchers have been looking for ways to destroy cancer cells in a targeted manner without further weakening the body. But for many patients whose immune system is severely impaired by chemotherapy or radiation, [...]
Older chemical libraries show promise for fighting resistant strains of COVID-19 virus
SARS‑CoV‑2, the virus that causes COVID-19, continues to mutate, with some newer strains becoming less responsive to current antiviral treatments like Paxlovid. Now, University of California San Diego scientists and an international team of [...]
Lower doses of immunotherapy for skin cancer give better results, study suggests
According to a new study, lower doses of approved immunotherapy for malignant melanoma can give better results against tumors, while reducing side effects. This is reported by researchers at Karolinska Institutet in the Journal of the National [...]
Researchers highlight five pathways through which microplastics can harm the brain
Microplastics could be fueling neurodegenerative diseases like Alzheimer's and Parkinson's, with a new study highlighting five ways microplastics can trigger inflammation and damage in the brain. More than 57 million people live with dementia, [...]
Tiny Metal Nanodots Obliterate Cancer Cells While Largely Sparing Healthy Tissue
Scientists have developed tiny metal-oxide particles that push cancer cells past their stress limits while sparing healthy tissue. An international team led by RMIT University has developed tiny particles called nanodots, crafted from a metallic compound, [...]
Gold Nanoclusters Could Supercharge Quantum Computers
Researchers found that gold “super atoms” can behave like the atoms in top-tier quantum systems—only far easier to scale. These tiny clusters can be customized at the molecular level, offering a powerful, tunable foundation [...]
A single shot of HPV vaccine may be enough to fight cervical cancer, study finds
WASHINGTON -- A single HPV vaccination appears just as effective as two doses at preventing the viral infection that causes cervical cancer, researchers reported Wednesday. HPV, or human papillomavirus, is very common and spread [...]
New technique overcomes technological barrier in 3D brain imaging
Scientists at the Swiss Light Source SLS have succeeded in mapping a piece of brain tissue in 3D at unprecedented resolution using X-rays, non-destructively. The breakthrough overcomes a long-standing technological barrier that had limited [...]
Scientists Uncover Hidden Blood Pattern in Long COVID
Researchers found persistent microclot and NET structures in Long COVID blood that may explain long-lasting symptoms. Researchers examining Long COVID have identified a structural connection between circulating microclots and neutrophil extracellular traps (NETs). The [...]
This Cellular Trick Helps Cancer Spread, but Could Also Stop It
Groups of normal cbiells can sense far into their surroundings, helping explain cancer cell migration. Understanding this ability could lead to new ways to limit tumor spread. The tale of the princess and the [...]
New mRNA therapy targets drug-resistant pneumonia
Bacteria that multiply on surfaces are a major headache in health care when they gain a foothold on, for example, implants or in catheters. Researchers at Chalmers University of Technology in Sweden have found [...]
Current Heart Health Guidelines Are Failing To Catch a Deadly Genetic Killer
New research reveals that standard screening misses most people with a common inherited cholesterol disorder. A Mayo Clinic study reports that current genetic screening guidelines overlook most people who have familial hypercholesterolemia, an inherited disorder that [...]
Scientists Identify the Evolutionary “Purpose” of Consciousness
Summary: Researchers at Ruhr University Bochum explore why consciousness evolved and why different species developed it in distinct ways. By comparing humans with birds, they show that complex awareness may arise through different neural architectures yet [...]
Novel mRNA therapy curbs antibiotic-resistant infections in preclinical lung models
Researchers at the Icahn School of Medicine at Mount Sinai and collaborators have reported early success with a novel mRNA-based therapy designed to combat antibiotic-resistant bacteria. The findings, published in Nature Biotechnology, show that in [...]
