Documentary highlights research on PIEZO proteins at MPL

Proteins are vital components of all living systems. They not only provide building blocks for structures and tissues, but perform essential functions, for example in metabolism, immune defense and internal communication. So-called PIEZO proteins play a decisive role in, among other things, the ability to perceive touch or pressure on the skin. Scientists at the Max Planck Institute for the Science of Light (MPL) and the Max-Planck-Zentrum für Physik und Medizin (MPZPM) are using specific optical methods to investigate how these work at the molecular level, which happens to be a featured topic of the latest episode of the program “Wissen hoch 2” on the channel 3sat.

PIEZO proteins are of great significance medically 

PIEZO proteins are essential for numerous physiological processes, including the regulation of blood pressure, the functioning of sensory neurons and homeostasis in tissues. They are also associated with pathophysiological conditions such as high blood pressure, osteoarthritis and mechanically induced pulmonary diseases. Studying them provides valuable insights into the mechanisms of mechanotransductive signaling, opening up new therapeutic possibilities. 

Mechanical stress triggers conformational changes

PIEZO proteins form tiny pores in the cell membrane. These mechanosensitive ion channels play a key role in the detection and transmission of mechanical stimuli, such as pressure or stretching. The change in pressure on the cell membrane causes a conformational change in the protein structure. This opens the membrane pores so that ions such as calcium (Ca²⁺) or sodium (Na⁺), can selectively flow into the cell. This ion influx in turn triggers an intracellular signal transduction cascade with corresponding response.

Tracking down the molecular mechanisms of the sense of touch 

Researchers at the “Nano-Optics” division at MPL, led by director Prof. Vahid Sandoghdar, are gaining insights into the complex and variable molecular structure of the PIEZO protein by observing it under a cryo-light microscope. The team is developing novel optical methods to study molecules and particles on the nanometer scale. A nanometer is one millionth of a millimeter in length. Measurement is conducted based on the ultra-precise detection of individual molecules. For this, scientists mark each protein with three fluorescent molecules which function like little flashlights to reveal their position and the three-dimensional structure of the protein. These molecules usually fade very quickly at room tempreature, making precise measurement more difficult. MPL researchers have developed a method that can drastically extend the lifespan of these color molecules by freezing the samples at temperatures close to absolute zero. In a complex technical process developed in-house, the PIEZO proteins are shock-frozen without their structure being destroyed in the freezing process. The molecules then have the property of going on and off randomly like little lighthouses. Scientists make use of this effect to determine the exact position of the molecules on the sub-nanometer scale. “The blinking reveals the actual structure of the proteins and how they change shape while the cell is active. This enables us to understand how this PIEZO protein actually works,” explains Hisham Mazal of Prof. Vahid Sandoghdar´s research division.

Electron microscopic investigations have shown that the PIEZO protein has two conformational states: open and closed. However, this method is not sensitive enough to decipher the exact processes taking place in the PIEZO protein. “It was the combination of the two approaches – fluorescence labeling and cryo-light microscopy – that revealed new nuances between the open and closed conformations,” says Prof. Vahid Sandoghdar. The scientists benefit from the high specificity of the labeling and the resolution of cryo light microscopy, which almost reaches molecular resolution. The field of research is still young, and thus holds correspondingly great potential for new observations. “We and thousands of other scientific groups are working to get findings that are very laborious to obtain. Only when you bring these findings all together can you learn a bit more.”


You can watch the complete episode, titled “Die Protein-Revolution”, here. The segment on PIEZO proteins and research at the MPL starts at 31:36 min (only available in German).

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