Nieng Yan: A platform that sharpens images of proteins under the microscope

Oct. 6, 2020

Molecular biology researchers have developed a technology to bring into view crisper images of individual proteins and other molecules using a highly advanced microscope.

The innovation, a new type of gridded platform that holds the protein sample still so that it freezes uniformly, promises to help researchers explore protein functions and activities. The platform works with a technology called cryogenic electron microscopy (cryo-EM), which has become one of the most powerful techniques to reveal the atomic structures and mechanisms of biological molecules.

Capturing images of very small features requires first freezing the proteins to quell normal molecular vibrations. Researchers place a small drop of solution containing millions of copies of a single protein on a grid to promote even freezing prior to imaging the sample with the microscope. The new grids contain graphene, a nanomaterial consisting of a single layer of carbon atoms. The uniform nature of the graphene grid enables the solution to freeze into a thinner ice layer with an increased protein density compared to existing grids, two factors that improve the resolution of the resulting images.

Nieng Yan and her team developed a convenient and inexpensive approach to fabricating the graphene grids that involves the application of ultraviolet light to generate ozone gas that gently oxidizes the surface. The fabrication process takes only a few hours, and hundreds of grids can be produced simultaneously. Graphene’s broad compatibility with a variety of other materials supports customized grid designs for specific proteins.

"The high quality of these graphene grids will be particularly useful for the studies of membrane protein structures and activities in their native environments.” – Nieng Yan

Innovator: Nieng Yan, the Shirley M. Tilghman Professor of Molecular Biology

Co-inventor: Postdoctoral research fellow Xiao Fan; Yimo Han, former Princeton postdoctoral researcher, now Assistant Professor of Materials Science and Nanoengineering at Rice University

Collaborators: Nan Yao, Senior Research Scholar, Princeton Institute for the Science and Technology of Materials, and Director of the Imaging and Analysis Center; Christopher Tully, Princeton Professor of Physics; Jing Kong, Professor of Electrical Engineering and Computer Science, Massachusetts Institute of Technology

Development status: Princeton is seeking outside interest for the development of this technology.

Funding: National Science Foundation, the Simons Foundation and the John Templeton Foundation

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Molecule with various atoms
A new method for preparing graphene-based grids for use in cryo-electron microscopy makes it possible to obtain sharper images of molecules such as this streptavidin protein. Image by Nieng Yan lab, Princeton University