An article published online today in Nature Methods describes the use of SOMAmer® reagents to specifically label and precisely visualize single molecules within single cells. This new use for SOMAmer reagents opens the door to viewing how biological structures are organized on a molecular scale and how they function in living tissue in real time.

The fundamental laws of physics prevent traditional light microscopy from resolving objects that are smaller than about 200 nm, the so-called “diffraction limit.” But biology happens on a much, much smaller scale: a protein such as hemoglobin is 5.5 nm wide and a DNA double helix is only 2 nm wide. The advent of “super-resolution microscopy” has allowed scientists to breach the diffraction limit and see inside cells at an unprecedented level of detail. To help orient the view, individual proteins within individual cells are commonly labeled with antibodies, which are then detected by fluorescent probes. However, antibodies are usually three or four times larger than their target proteins, so the position of the antibody rather than the protein of interest is what’s seen in the image.

In the Nature Methods paper, a team of scientists from Ludwig Maximilian University of Munich, Max Planck Institute of Biochemistry, the European Molecular Biology Laboratory (EMBL), and SomaLogic substituted SOMAmers for antibodies as labeling reagents for the super-resolution microscopy technique known as “DNA Points Accumulation in Nanoscale Topography” (DNA-PAINT). SOMAmers — modified aptamers that bind tightly and specifically to protein targets — are approximately a tenth of the size of antibodies. Using SOMAmers, the investigators were able to resolve the membrane receptor protein EGFR to less than 8 nm, an approximate two-fold improvement over labeling using conventional antibodies. They also demonstrated that SOMAmers could provide quantitative information on the number of target proteins present, simultaneously label multiple cellular proteins, image proteins inside cells, and image proteins on living cells.

According to the investigators, “SOMAmers should make it possible to eventually image tens to hundreds of cellular targets in single cells with single-molecule spatial resolution in a quantitative fashion and furthermore allow for live labeling and imaging of membrane-bound proteins.”

Reference: Strauss, S et al. (2018) “Modified aptamers enable quantitative sub-10-nm cellular DNA-PAINT imaging” Nature Methods, https://doi.org/10.1038/s41592-018-0105-0

See also a news story from Ludwig Maximilian University of Munich.