AsianScientist (Oct. 25, 2018) – In a study published in Nature Communications, scientists in Japan have developed a method to track hundreds of thousands of single molecules within living cells in a short span of time.
The ability to track individual molecules within living cells would be a boon to biomedical research and drug discovery. By observing the behavior of and interactions between molecules within subcellular components, over time and across varying conditions, researchers can better understand fundamental cellular biology and perhaps develop better drugs.
In the present study, a research team from Osaka University and RIKEN has developed a system that can automatically search for, focus on, image and track single molecules within living cells. The team relied on an artificial intelligence (AI)-based system which involved training neural networks to focus correctly on a sample and search for cells without human intervention. The AI would then track single fluorescent molecules visualized with a total internal reflection fluorescence microscope.
The team tested their AI-based system on a receptor protein called EGFR, which is free to move along the plasma membrane of cells. The behavior and location of the protein depends on whether the protein has been modified by molecular tags. The researchers demonstrated that their system could differentiate between modified and unmodified states by tracking the movements of single receptors.
“We used the results obtained by our system to calculate pharmacological parameters, such as those reflecting the efficacy of drugs and the speed with which molecules diffuse away from their initial location,” said corresponding author Professor Masashiro Ueda of Osaka University. “The findings matched the values obtained in earlier studies using traditional labor-intensive methods, supporting the value of this system.”
“A major benefit of this approach is that the effects of ligands and inhibitors on a target can be quantified at the single-molecule level,” Ueda added. “The automation provided by this approach means that a large number of targets exposed to such molecules can be characterized at low cost, increasing the reliability of the results.”
In the future, the team hopes to apply this system to the monitoring of single molecules elsewhere in the cell, such as in the nucleus and organelles, and using other optical microscopes. The system should also be applicable clinically for reliable genome-wide screening and pharmacological testing, said the researchers.
The article can be found at: Yasui et al. (2018) Automated Single-Molecule Imaging in Living Cells.
Source: Osaka University; Photo: Shutterstock.
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