A Raman-Based Method to Explore Protein Phase Separation
Geneva, February, 25th 2026 - Dr Pierrick Berruyer.
A study from the groups of Prof. Bordignon and Prof. Adachi, published in The Journal of Physical Chemistry Letters, introduces a new approach to investigate liquid–liquid phase separation (LLPS) in protein systems. Exploiting the advantages of in-situ Raman microspectroscopy, the researchers provide a method to directly measure protein concentrations in heterogeneous samples and construct complete phase diagrams from minimal sample volumes.
Video - Compilation of protein condensate formation. Full video available from Supplementary Information of the original article.
Liquid–liquid phase separation (LLPS) is a fundamental process in which a homogeneous mixture spontaneously separates into two liquid phases, a protein-rich or dense phase and a dilute or light phase. In several cellular processes, protein LLPS enables the formation of distinct, separate regions without the need to create a physical membrane. This phenomenon helps cells to rapidly organize their internal behaviour in response to environmental changes, by allowing the reversible formation of a high concentration of protein at a specific location.
In some cases, if LLPS does not occur properly or is disturbed, this can lead to the development of diseases such as neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease. There is therefore significant interest in learning more about LLPS in order to improve descriptions of this biophysical process and better understand how it is involved in certain disease mechanisms. Moreover, a better understanding of the process is essential to support the development of emerging therapeutic strategies targeting LLPS.
Researchers from the Department of physical chemistry, School of chemistry and biochemistry, Faculty of science at UNIGE have developed a new method to explore the physical conditions underlying LLPS formation and to map the internal composition of the system in which it occurs. Using in-situ Raman microspectroscopy, the UNIGE team directly measured protein and cosolute concentrations inside and outside the droplets as the temperature changes and constructed complete phase diagrams from a single small sample under different environmental conditions. This approach could help improve our understanding of biomolecular condensates and support future drug discovery efforts.
The full article is published in The Journal of Physical Chemistry Letters.
Illustration credits of the article block on the School's homepage: stock.adobe.com / Design Cells
25 Feb 2026