Pressure and Osmolyte Effects on Liquid-Liquid Phase Separation Phenomena and Condensates of Proteins

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In recent years, liquid-liquid phase separation (LLPS) phenomena have been recognized to play an important role in the membrane-less compartmentalization of cells through the formation of biomolecular condensates. Using UV/Vis, CD, FTIR spectroscopies, phase-contrast light and fluorescence microscopy techniques, we plan to study the combined effects of temperature, pressure and natural osmolytes on LLPS phenomena of different types of such condensates, focusing essentially on the effect of pressure up to the kbar-regime. First studies of our group have shown, quite unexpectedly, that liquid-liquid phase transitions of proteins are among the most pressure sensitive processes found in Nature. Hence, organisms thriving at high-pressure conditions in the deep sea, where pressures up to 1 kbar regime are encountered, have to cope with this high pressure-sensitivity of biomolecular condensates, probably utilizing particular osmolytes. We will then scrutinize the effectiveness of such membrane-less compartments under extreme environmental conditions in modulating the partitioning, conformational dynamics, self-assembly, and activity of peptides and nucleic acids. As life probably started in the deep sea, this knowledge will also shed light on the possible evolutionary advantages of utilizing LLPS for biological function and provide insights into the self-organization principles underpinning cellular evolution in the face of external stresses.