New technology described in a study published today in the open access journal Journal of Biology makes it possible to image and quantify molecules within individual mammalian or bacterial cells. Claude Lechene and colleagues describe the development of multi-isotope imaging mass spectrometry (MIMS), which has applications in all fields of biology and biomedical research.
“This method allows us to see what has never been seen before, and to measure what has never before been measured,” Lechene says. “Imagine looking into a building, slice by slice. You can see not only that it contains apartments, but also that each apartment contains a refrigerator. You can see that there are tomatoes in the refrigerator of one apartment, and potatoes in the refrigerator of another. You can count how many there are and measure how fast they are used and replaced. It is this level of resolution and quantification that MIMS makes possible within cells.”
Lechene, of Harvard Medical School and Brigham and Women’s Hospital in the US, worked with colleagues from around the world to develop and test the new methodology.
A beam of ions is used to bombard the surface atoms of the biological sample, and a fraction of the atoms are emitted and ionized. These “secondary ions” can then be manipulated with ion optics – in the way lenses and prisms manipulate visible light - to create an atomic mass image of the sample. Lechene et al. developed MIMS by combining the use of a novel secondary-ion mass spectrometer developed by Georges Slodzian, from the Université Paris-Sud in France, labeling with stable isotopes and building quantitative image-analysis software.
MIMS can generate quantitative, three-dimensional images of proteins, DNA, RNA, sugar and fatty acids at a subcellular level in tissue sections or cells. “Using MIMS, we can image and quantify the fate of these molecules when they go into cells, where they go, and how quickly they are replaced,” says Lechene.
The method does not need staining or use of radioactive labelling. Instead, it is possible to use stable isotopes to track molecules. For example, researchers could track stem cells by labelling DNA with 15N. “These stable isotopes do not alter the DNA and are not toxic to people; with MIMS and stable isotope labelling we could track these cells, where they are and how they have changed several years later,” says Lechene.
“The most significant feature of this technique is that it opens up a whole new world of imaging; we haven’t yet imagined all that we can do with it,” says Peter Gillespie from the Oregon Health and Science University in Portland, USA in an accompanying news article, also published today in Journal of Biology.
Lechene et al. describe how they developed MIMS, and illustrate some potential applications for biomedical research. For example, the article describes using MIMS to track donor spleen cells in the lymph nodes of a mouse, suggesting that MIMS may have applications in tracking stem cells and in understanding why some organ transplants are rejected. In another example MIMS was used to measure the capture of atmospheric nitrogen and its conversion to dietary nitrogen within single bacteria, a phenomenon essential to supporting life on earth.
The accompanying news article, published today in Journal of Biology, includes an interview with Lechene and garners views from researchers about the implications and applications of Lechene et al.’s article. Speaking with science writer Jonathan Weitzman, Brad Amos of the MRC Laboratory of Molecular Biology in Cambridge UK said “The labelling of the lymph node cells by 15N...suggests that MIMS may be highly useful in immunology and cancer research. This may turn out to be a key paper in the development of a really important imaging method.” Weitzman writes, ‘[Gillespie] agrees with Amos that the technology represents an imaging revolution. “The novelty of the technique means it will take some time for the details to be absorbed, [but it] sets a spectacular new standard for spatial resolution and detection of stable and radioactive compounds in cells.”
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