| Using nanopore DNA sequencing technology, researchers from TU Delft and the University of Illinois have managed to scan a single protein: by slowly moving a linearized protein through a tiny nanopore, one amino acid at the time, the researchers were able to read off electric currents that relate to the information content of the protein. | |
| The researchers published their proof-of-concept in Science (“Multiple re-reads of single proteins at single-amino-acid resolution using nanopores”). The new single-molecule peptide reader marks a breakthrough in protein identification, and opens the way towards single-molecule protein sequencing and cataloguing the proteins inside a single cell. |
| Proteins are the workhorses of our cells, yet we simply don’t know what proteins we all carry with us. A protein is a long peptide string made of 20 different types of amino acids, comparable to a necklace with different kinds of beads. From the DNA blueprint, we are able to predict of which amino acids a protein consists. | |
| However, the final protein can greatly differ from the blueprint, for example due to post-translational modifications. Current methods to measure proteins are expensive, limited to large volumes, and they cannot detect many rare proteins. | |
| With nanopore-based technology, one is already able to scan and sequence single DNA molecules. The team led by Cees Dekker (TU Delft) now adapted this technique to instead scan a single protein, one amino acid at a time. | |
| “Over the past 30 years, nanopore-based DNA sequencing has been developed from an idea to an actual working device,” Cees Dekker explains. “This has even led to commercial hand-held nanopore sequencers that serve the billion-dollar genomics market. In our paper, we are expanding this nanopore concept to the reading of single proteins. This may have great impact on basic protein research and medical diagnostics.” | |
Like beads down the drain |
|
| The new technique reveals characteristics of even single amino acids within a peptide, but how? Lead author of the paper Henry Brinkerhoff, who pioneered this work as a postdoc in Dekker’s lab, explains: “Imagine the string of amino acids in one peptide molecule as a necklace with different-sized beads. Then, imagine you turn on the tap as you slowly move that necklace down the drain, which in this case is the nanopore. If a big bead is blocking the drain, the water flowing through will only be a trickle; if you have smaller beads in the necklace right at the drain, more water can flow through. With our technique we can measure the amount of water flow (the ion current actually) very precisely.” | |
| Cees Dekker enthusiastically adds: “A cool feature of our technique is that we were able to read a single peptide string again and again: we then average all the reads from that one single molecule, and thus identify the molecule with basically 100% accuracy.” | |
| This results in a unique read-off which is characteristic for a specific protein. When the researchers changed even one single amino acid within the peptide (‘a single bead within the necklace’), they obtained very different signals, indicating the extreme sensitivity of the technique. The group led by Alek Aksimentiev at the University of Illinois performed molecular dynamics simulations that showed how the ion current signals relate to the amino acids in the nanopore. | |
Scanning the barcode for identification |
|
| The new technique is very powerful for identifying single proteins and mapping minute changes between them – much like how a cashier in the supermarket identifies each product by scanning its barcode. It also may provide a new route towards full de novo protein sequencing in the future. | |
| Henry Brinkerhoff clarifies: “Our approach might lay a basis for a single-protein sequencer in the future, but de novo sequencing remains a big challenge. For that, we still need to characterize the signals from a huge number of peptides in order to create a ‘map’ connecting ion current signals to protein sequence. Even so, the ability to discriminate of single-amino-acid substitutions in single molecules is a major advance, and there are many immediate applications for the technology as it is now…..” |
News
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 [...]
New skin-permeable polymer delivers insulin without needles
A breakthrough zwitterionic polymer slips through the skin’s toughest barriers, carrying insulin deep into tissue and normalizing blood sugar, offering patients a painless alternative to daily injections. A recent study published in the journal Nature examines [...]
