. Scientific Frontline: How protein-rich droplets form

Friday, February 10, 2023

How protein-rich droplets form

Martina Havenith-Newen has gained new insights by combining two methods.
Photo Credit: © RUB, Marquard

Terahertz spectroscopy can be used to explain the spontaneous formation of protein-rich droplets, which may lead to neurodegenerative diseases.

With the help of a new method, terahertz calometry, it is a research team of the Bochum Cluster of Excellence Ruhr Explores Solvation RESOLV succeeded in re-examining the spontaneous phase separation into a protein-rich and a low-protein phase in one solution. It is believed that the protein-rich droplets favor the formation of neurotoxic protein aggregates - a starting point for neurodegenerative diseases. The researchers around Prof. Dr. Martina Havenith, holder of the Chair for Physical Chemistry II at the Ruhr University Bochum, reports in the Journal of Physical Chemistry Letters from 6. February 2023.

Molecular level and time resolution in the picosecond range

The study is based on the work in the Terahertz-Calorimetry project, which was funded by the European Research Council with an Advanced Grant. "The visionary idea in the project was to marry two powerful techniques in physical chemistry - laser spectroscopy and calorimetry -" explains Grantee Martina Havenith.

Calorimetry measures the basic parameters for chemical and biochemical reactions such as heat capacity, enthalpy and entropy. Knowing these substance-specific quantities can be used to predict whether, for example, a reaction will take place spontaneously without the addition of energy, or whether there are equilibrium conditions. Calorimetric measurements take place in a macroscopic container. The amounts of heat required for chemical or biochemical reactions are measured. "The limitation of this method lies in its limited time resolution and the required number of samples," says Martina Havenith.

Her ERC project was about circumventing these limitations. This required a new approach in order to be able to measure calorimetric quantities for the smallest samples with a time resolution of picoseconds, i.e. a millionth of a millionth of a second, at a molecular level. "In principle, however, we cannot achieve time and location resolutions in this area with the traditional concept of heat measurements," explains the researcher. “This required a revolutionary approach that offers a different approach intrinsically."

Water plays a crucial role

Her working group was able to show that measurements of absorption in the so-called terahertz range can measure spectroscopic fingerprints, which are linearly correlated with calorimetric quantities. This enables researchers to track these fundamental basic calorimetric variables in real time using spectroscopic and ultra-fast laser spectroscopic methods, even with complex systems, during a process or a reaction.

In their current work, they use this method - inspired by the collaboration with the working groups of Prof. Dr. Konstanze Winklhofer and Prof. Dr. Jörg Tatzelt at the Ruhr University for the first time on a highly topical topic in biomedical research: They examined the liquid-liquid phase separation, the spontaneous phase separation into a protein-rich and a low-protein liquid phase.

“By means of terahertz calorimetry, the formation of these protein-enriched droplets can be re-rolled at the molecular level. Not only the proteins themselves, but above all the water plays a crucial role,” reports Martina Havenith. “We can now follow the changes in the water live with the Terahertz camera in the development process and, based on the derived calorimetric quantities, make precise predictions about the formation and its dependence on external parameters such as temperature."

Funding: The work was supported by the European Research Council Advanced Grant 695437 THz-Calorimetry, the German Research Foundation as part of the RESOLV EXC2033-390677874 Cluster of Excellence, the Mercator Research Center, the European Union (FP-RESOMUS - MSCA 801459) as well as the Federal Ministry of Education and Research and the Ministry of Culture and Science of the State of North Rhine-Westphalia.

Published in journalJournal of Physical Chemistry Letters

Research Material:

1. Angewandte Chemie International Edition


Source/CreditRuhr University Bochum

Reference Number: chm021023_02

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