Simultaneous imaging of proteins in a single cell

Researchers from Daegu Gyeongbuk Institute of Science and Technology (DGIST) have developed an innovative method that allows them to visualise up to tens of different proteins simultaneously in the same cell. Described in the journal ACS Applied Materials & Interfaces, the technology could help scientists elucidate the complex protein interactions involved in degenerative diseases, deepening our understanding of their mechanisms and allowing for early detection and treatment.

Degenerative diseases such as Alzheimer’s often involve complex interactions between multiple proteins and other biomolecules. Understanding these interactions using existing imaging technologies is difficult because of insufficient resolution and the impossibility of simultaneously detecting many different proteins.

In a recent interdisciplinary study, a research team led by DGIST Professors Dae Won Moon and Su-Il In developed an innovative approach that extends the applications of secondary-ion mass spectrometry from its original purpose in the semiconductor industry to the biomedical imaging field. Secondary-ion mass spectrometry allows one to analyse the composition of surfaces and offers very high resolution, but using this technology to image proteins was until now considered impossible.

In the researchers’ novel approach, different metal oxide nanoparticles are individually attached to antibodies that bind to specific target proteins. The mass spectrometer can easily detect these nanoparticles even at low irradiation doses, which leaves the cell tissue intact and allows for multiple analyses on the same cells.

Through this approach, it is theoretically possible to analyse tens of proteins simultaneously. This vastly surpasses existing fluorescence-based approaches, which allow for the simultaneous imaging of around four proteins.

The researchers used their method to compare the distribution of proteins in the brain tissue of mice that were either healthy or had Alzheimer’s. They showed that valuable insight could be gained from observing multiplex protein distributions in the hippocampus, and demonstrated how these differed between healthy and diseased mice.

“We can now visualise multiple proteins on cell membranes with a spatial resolution of 300 nm,” Prof Moon said. He expects this new imaging approach to become an important tool to deepen our understanding on degenerative diseases.

“The proposed technique could be used to figure out the early stages of Alzheimer’s disease, in turn allowing for early detection and treatment.”

Image caption: Professor Dae Won Moon, Young-Ho Park and Professor Su-Il In. Beside them is a secondary-ion mass spectrometer, a device used in the semiconductor industry that, as the researchers demonstrate, holds tremendous potential in biomedical imaging.

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