Credit: Gerti Beliu, DALL-E 3 / University of Würzburg
A team of researchers at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, have developed a novel biocompatible molecular ruler. Providing a means for resolving the true resolution of super-resolution microscopy could provide unprecedented advancements in the fields of medical and biological imaging.
Super-resolution microscopy achieves optical resolution in the nanometer range, however, until now that resolution has proved difficult to verify in applications such as multiprotein complexes due to the lack of biomolecular reference systems that could be accurately labeled at the nanometer scale. With the creation of the PicoRulers (Protein-based Imaging Calibration Optical Rulers), researchers can now verify the resolution of super-resolution microscopy in various applications.
The researchers utilized click chemistry and genetic code expansion to develop these novel molecular rulers. The PicoRulers are designed based on three-part protein PCNA and with the addition of unnatural amino acids at precise positions the protein can be modified in a way that dyes can be added with minimal linkage error. In the research, published in Advanced Materials, the researchers demonstrated the ability of the PicoRulers to provide unprecedented precision for verifying the resolution of super-resolution microscopy on biomolecules.
"The ability to resolve real biological structures at sub-10-nanometre level marks a new era in biological imaging. Compared to previously used artificial macromolecules, our PicoRulers are not only characterised by their biological compatibility. They also enable unrivalled precision for testing resolution under realistic conditions," said Professor Markus Sauer.
Further development of PicoRulers could drive new advancements in medical and biological imaging by providing a method to validate and improve the resolution of current and new super-resolution microscopy methods.
"Our PicoRulers are not only a tool for more precise measurements, but also open the door to a deeper and more detailed investigation of complex processes that take place within our cells," said Dr. Gerti Beliu.