by Meike Drießen, Ruhr-Universitaet-Bochum, edited by Lisa Lock, reviewed by Robert Egan

Dynamical fingerprints of biomolecules in terahertz (THz) spectroscopy from hydration water to protein modes. Credit: Nature Reviews Chemistry (2025). DOI: 10.1038/s41570-025-00712-8

Researchers from Ruhr University Bochum, Germany, have developed a new method that allows them to visualize the contribution of the interaction between water and proteins for the first time with extreme temporal resolution. Terahertz (THz) calorimetry makes it possible to quantify changes of fundamental thermodynamic magnitudes, such as solvation entropy and enthalpy in relation to biological processes in real time.

The researchers under Professor Martina Havenith, spokeswoman for the Excellence Cluster Ruhr Explores Solvation¨CRESOLV, published their report in the journal Nature Reviews Chemistry on May 9, 2025.

Fundamental biological processes, like the formation of fibrils¡ªfine, thread-like structures made from bundles of protein filaments that serve as a major component of various tissues and cells¡ªor the folding of proteins or protein aggregation as a sign of neurological diseases, are non-equilibrium processes.

"This means that they can be initiated by minor changes in external conditions, such as temperature," explains Havenith. Although all these processes occur in a solvent¡ªin this case, water¡ªthe interaction with the water molecules was previously neglected.

With terahertz calorimetry, Havenith and her team have developed a method that makes it possible to quantitatively deduce thermodynamic magnitudes that determine the course of biological functions from spectroscopic measurements.

Connecting fundamental solvation thermodynamics concepts with terahertz spectroscopic observables. Credit: Nature Reviews Chemistry (2025). DOI: 10.1038/s41570-025-00712-8

New frequency range utilized

"This allows us, for the first time, to measure spectroscopically the thermodynamics of the interaction between proteins and water," says the researcher. The team is conducting measurements in the terahertz range of the electromagnetic spectrum, which was previously not accessible experimentally.

With precise spectroscopic measurements and a new theoretical concept, the researchers were able to discover a 1:1 correlation between the spectroscopic measurement data and thermodynamic quantities, such as heat capacity or free energy.

This makes it possible to utilize all the benefits of laser-spectroscopic methods in the future. "We can now use extreme temporal resolution of a millionth of a millionth of a second to examine thermodynamic equilibration in chemical reactions in real time for the first time," says Havenith. Measurements in the smallest nanocontainers and local hot spots during the formation of neurotoxic aggregates are now within reach.

More information: Simone Pezzotti et al, Terahertz calorimetry spotlights the role of water in biological processes, Nature Reviews Chemistry (2025). DOI: 10.1038/s41570-025-00712-8