This will open up new possibilities for sequencing DNA, proteins and their post-translationally modified biomolecules, and is expected to be used for gene sequencing and diagnostic biomarker detection.
Editor’s note: This article is from WeChat public account “MEMS” (ID: MEMSensor ), author Memes Consulting Yin Fei, the original title “pretend to be a block of “muscle”, Fudan University developed a new injection implant sensor”, slightly cut.
Some types of bacteria have the ability to “punch” other cells and then kill them. These bacteria form a specialized channel called the pore-forming toxin (PFT), which is then attached to the cell membrane of the target cell to form a tubular passage through the cell membrane. This structure that penetrates the cell membrane is a so-called pore. By punching through multiple PFTs, the target cells will self-apoptosis.
However, researchers’ interest in PFT goes far beyond bacterial infection. Nanopores formed by their “punching” can also be used for biomolecular sensing: biomolecules (such as DNA or RNA) can pass through these nanopores as a voltage-controlled line, such as in DNA Nucleic acids) are capable of providing a unique electrical signal that can be read. In fact, nanopore sensing has been marketed as an important tool for DNA or RNA sequencing.
According to the James Consulting, a study led by Matteo Dal Peraro, a scientist at the EPFL in Lausanne, recently published in Nature Communications, they studied another important PFT that can be effectively used for more complex Sensing applications such as protein sequencing. The PFT they studied was aerolysin, produced by Aeromonas hydrophila bacteria, and was the “founding member” of the PFT major family found in many organisms.
One of the main advantages of aerolysin is that it forms very narrow pores that are much higher than the “resolution” of other toxins. Previous studies have shown that lysin can be used to “perceive” a variety of biomolecules, but little research has been done on the relationship between the composition of the gas lysin and its molecular sensing capabilities.
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The researchers first studied the structure by computer simulation using a structural model of aerolysin. Aerolysin is a protein composed of amino acids. This model helps scientists understand these amino acids.How to affect the function of aerolysin.
After the researchers grasp the relationship between their structure and function, they can strategically change the amino acids in the computer model. The model was then used to predict the possible effects of each structural change on the overall function of the aerosol.
By calculating, Dr. Chan Cao, the lead author of the study, acquired 16 genetically engineered “mutant” aerolysin pores and embedded them into two-layer lipids to mimic their role in the cell membrane, and then Various measurements (single channel recording and molecular translocation experiments) were performed to understand how to modulate the ionic conductivity, ion selectivity and translocation characteristics of the gas lysin pores at the molecular level.
In this way, the researchers finally found a factor that affects the relationship between the structure and function of the gas-soluble hormone: the gas-soluble “cap”. It has been found that the gas lysin pores are not only channels that pass through the cell membrane, but also have a cap-like structure that attracts and binds the target molecules and “pushes” them through the channels. In addition, it is the static electricity in the region of the gas soluble cap that affects the “pull” molecule.
“By understanding how the structure of the gas-soluble pores affects its function, we can now design custom pores for different sensing applications,” Dal Peraro said. “This will be for sequencing DNA, proteins and their post-translational modifications. Biomolecules open up new possibilities and are expected to be used for gene sequencing and diagnostic biomarker detection.”
At present, researchers have applied for patents for the sequencing and characterization of this genetically engineered aerosol lysin.