Facing a camera, Margot Riggi (Biologist, postdoc in the Loewith & Roux labs, UNIGE) and Karolina Niewola (former postdoc in the Loewith lab, UNIGE) present their recent work and give emphasis on the biochemical problem behind it. Adai Colom Diego (postdoc in the Roux lab, UNIGE) comments with a few lines to explain the biological approach used to solve the problem. They are from different disciplines but meet through chemical biology.
Perspective by Dr. Adai Colom Diego
Composed of a phospholipid bilayer, the cell membrane is a selective barrier enclosing the different cell organelles, separating the interior of the cell from the environment and performing multiple roles (phagocytosis, signaling, communication, pinocytosis, etc.). Beyond these biochemical properties, the membrane relies on different physical mechanical properties, an important one being the membrane tension, which plays an essential role in numerous cell processes such as cell migration, cell division, and phagocytosis.
Membrane tension remains however notoriously difficult to measure in living cells, especially on intracellular membranes such as organelles, as in this case it is limited membrane accessibility from the outside of the cell which requires either to pull or push it using an optical tweezers or an atomic force microscopy. These methods are widely used to measure the mechanical properties of cells, and both having similar limitations. For this reason, Stefan Matile’s group developed non-invasive fluorescent probes (commercialized by Spirochrome under the name: Flipper-TR) that allow the measurement of the membrane tension in living cells using fluorescent lifetime imaging microscopy (FLIM). FLIM measures the conformational state of the probe, which depends on the lateral pressure of the membrane.
We have shown the linear dependency between the fluorescent lifetime of the probe and the membrane tension (a high membrane tension is translated into high lifetime signal while a low tension reduces the lifetime) which relies on a membrane-tension-dependent lipid phase separation, as described in the video. It is thanks to this phenomenon, that in the same membrane two different processes can occur, one which needs a high membrane tension (e.g. endocytosis) and at same time a second one which needs a low membrane tension (e.g. vesicle fusion). For the first time, we will have the opportunity to study the role of the membrane tension during a critical cell process, as well to target the probe inside the cell so as to observe the role of membrane tension there, in particular in organelles such as mitochondria, endoplasmic reticulum and lysosomes.
Adai Colom, Emmanuel Derivery, Saeideh Soleimanpour, Caterina Tomba, Marta Dal Molin, Naomi Sakai, Marcos González-Gaitán, Stefan Matile & Aurélien Roux, “A fluorescent membrane tension probe”, Nature Chemistry, 2018. Read the publication
Margot Riggi, Karolina Niewola-Staszkowska, Nicolas Chiaruttini, Adai Colom, Beata Kusmider, Vincent Mercier, Saeideh Soleimanpour, Michael Stahl, Stefan Matile, Aurélien Roux & Robbie Loewith, “Decrease in plasma membrane tension triggers PtdIns(4,5)P2 phase separation to inactivate TORC2”, Nature Cell Biology, 2018. Read the publication
How to get the Flipper-TR?
The Flipper-TR is commercialized by Spirochrome.