A research team at the Max Planck Institute for the Science of Light (MPL) has made significant progress in the study of proteins. Under the direction of Prof. Vahid Sandoghdar, the Nanooptics department developed a method that makes it possible to image the mechanosensitive protein PIEZO1 in its native cell membrane environment with Ångström accuracy. This new technique of cryo-optical microscopy, published in a recent study, promises to revolutionize the understanding of the structure and function of membrane proteins.

Proteins such as PIEZO1, which are located in the cell membrane and serve as sensors for touch and pressure, are essential for central biological processes. However, traditional methods such as X-ray diffraction or cryo-electron microscopy (cryo-EM) reach their limits: the former requires crystallized samples, while the latter often offers only low contrast in complex cellular environments. The MPL team’s new method uses optical microscopy under cryogenic conditions (8 K) to image PIEZO1 in a near-native state. Using fluorescent markers, the team was able to visualize the dome-like structure of the protein with its three “wings” and visualize different configurations that show how PIEZO1 deforms under mechanical stress.

The key to success was a special process of rapid freezing in liquid cryogen, which keeps the protein structure intact by preventing the crystallization of water molecules. A specially developed apparatus, consisting of a cryogenic optical microscope and a vacuum shuttle, ensures that the sample remains cold and has no air contact during the experiment. This technique significantly extends the life of the fluorescent markers, which allows more photons to be collected and the position of the markers to be determined with a precision of a few angstroms – about the size of individual atoms.

The method opens up new possibilities in structural biology, especially for the study of membrane proteins in their native environment. The team plans to combine the technique with high-resolution cryo-EM to gain even more precise insights into the molecular mechanisms of life. This approach could change basic research in the long term and advance the quantitative understanding of biological processes.

Original Paper:

Cryo–light microscopy with angstrom precision deciphers structural conformations of PIEZO1 in its native state | Science Advances

Editor: X-Press Journalistenbüro GbR

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