"This technique has the potential to revolutionize microscopy, but its biomedical applicability is still in its infancy." Beliu explains. At this point he and his research group would like to start, to better understand the basics of the method and make it more extensively applicable. In the future, Beliu believes an application in the medical field is possible.
In high-resolution fluorescence microscopy, a resolution of less than 10 nanometers (a nanometer (nm) is a millionth of a millimeter) is now possible, making it about 50 times sharper than conventional light microscopy. In microscopy, to make a particular protein visible, it is usually labeled with two antibodies that bind to each other and to which a fluorescent dye is attached. An antibody is between 10 and 15 nm in size, resulting in the fluorescent signal being up to 30 nm adjacent to the actual labeled site. The click chemistry used by Beliu involves the addition of a specific chemical structure to a single biomolecule, such as a single amino acid (the basic components of a protein). "Now the dye can bind to this artificial amino acid directly, without antibodies, like matching puzzle pieces. This permits much sharper images, and you can, for example, identify small proteins that are right next to each other, which you would not have been able to distinguish at all with antibodies," says Beliu.
The use of click chemistry has other advantages apart from better structural resolution. For example, the binding of the two "puzzle pieces" is very specific and does not interfere with the normal processes in the cell due to its special chemical structure. This is an important prerequisite for medical application with few to no side effects. For example, due to their rapid cell division, cancer cells absorb certain biomolecules more effectively than other cells. The "clickable" chemical structures can be attached to these compounds, which are highly accumulated in the cancer cells. If the second "puzzle piece" of the click chemistry is attached to a drug, it can be used to fight cancer cells very effectively. "However, there are still some basic research questions that need to be addressed before there is a broad medical application. That's exactly what we want to tackle," Beliu explains.
MEDICA-tradefair.com; Source: Rudolf-Virchow-Zentrum – Center for Integrative and Translational Bioimaging