Researchers at the Daegu Gyeongbuk Institute for Science and Technology have developed innovative methods that allow them to visualize up to dozens of different proteins in the same cell at the same time.
This technology can help scientists understand the interaction of complex proteins in degenerative diseases such as Alzheimer’s, deepen our understanding of their mechanisms, and enable early detection and treatment.
Degenerative diseases such as Alzheimer’s often involve complex interactions between several proteins and other biomolecules.
Understanding this interaction using existing imaging technology is difficult because of the lack of resolution and the inability to detect many different proteins at the same time.
With this new approach, various metal oxide nanoparticles are individually bound to antibodies that bind to specific target proteins. Mass spectrometers can easily detect these nanoparticles even at low radiation doses, which means that cell tissue remains intact and multiple analyzes of the same cell are possible.
With this approach, it is theoretically possible to analyze dozens of proteins simultaneously. This goes far beyond the existing fluorescence-based approach, which allows simultaneous imaging of around four proteins.
The researchers used their method to compare the distribution of protein in brain tissue in mice that were healthy or suffering from Alzheimer’s.
They show that valuable insights can be obtained by observing the multiplex distribution of proteins in the hippocampus of the brain, and how they differ between healthy and sick mice.
A combination of knowledge from various disciplines is needed to achieve this result. Moon commented: “For me, the special focus of this work is the collaboration of many researchers with different backgrounds, such as chemists, nanoparticles, doctors and biologists.
It’s not easy and takes a long time, but it’s fun to see progress.
We can now visualize some proteins in cell membranes with a spatial resolution of 300 nanometers. “He hopes this new imaging approach will become an important tool to deepen our understanding of degenerative diseases.
“The proposed technique can be used to identify the early stages of Alzheimer’s disease, which in turn allows early detection and treatment,” he said.
Reference: Dae Won Moon*1, Young Ho Park2, Sun Young Lee1, Heejin Lim1, SuHwa Kwak3, Minseok S. Kim1, Hyunmin Kim4, Eunjoo Kim4, Yebin Jung5, Hyang-Sook Hoe6, Sungjee Kim5, Dong-Kwon Lim7, Chul-Hoon Kim8, and Su-Il In*2 , Title of original paper: Multiplex Protein Imaging with Secondary Ion Mass Spectrometry Using Metal Oxide Nanoparticle-Conjugated Antibodies Journal: ACS Applied Materials & Interfaces DOI: https://dx.doi.org/10.1021/acsami.9b21800