More Than Just Viscous: Researchers Study the Movement of Proteins

07.08.2026

A study conducted at the European XFEL international research facility has yielded new insights into the movement of proteins in cell-like environments. The findings have now been published in the journal *Proceedings of the National Academy of Sciences*. The first author is Michelle Dargasz, a doctoral student at the University of Siegen.

Michelle Dargasz (Erstautorin der Studie, rechts) und Nimmi Das Anthuparambil (Zweitautorin, links) am „Materials Imaging and Dynamics“ (MID)-Instrument des European XFEL, wo die Experimente durchgeführt wurden.

Michelle Dargasz (first author of the study, right) and Nimmi Das Anthuparambil (second author, left) at the “Materials Imaging and Dynamics” (MID) instrument at the European XFEL, where the experiments were conducted.

How do proteins find their way through the dense crowd inside a cell? An international research team, including researchers from the University of Siegen, investigated this question at the world’s largest X-ray laser facility—the European XFEL. The results of the measurements show that it is not only the viscosity of the environment that matters. The way the molecules interact with one another also plays an important role—and can even cause individual proteins to move faster than expected under certain conditions. The study has now been published in the prestigious journal *Proceedings of the National Academy of Sciences* (PNAS).

“Conducting research at the European XFEL was a fantastic opportunity and a great experience. Since proteins are very small—we’re talking nanometers here—short-wavelength X-rays are well-suited for studying them,” says Michelle Dargasz, first author of the study and a doctoral student under Christian Gutt, professor of solid-state physics at the University of Siegen.

Proteins perform vital tasks within cells: they control chemical reactions, transmit signals, and interact with other proteins. For this to work, they must move through the densely packed interior of the cell. It is well known that the viscosity of the surrounding environment influences the movement of proteins. However, the study by Dargasz and her colleagues shows that other effects also play a decisive role.

For their experiments, the researchers used the protein ferritin, which is found in nearly all living organisms and stores iron. They added various substances to the aqueous protein solution to mimic the dense interior of a cell—ranging from small sugar molecules to large, branched polymer molecules.

At the European XFEL, the researchers were able to track the movement of the proteins using high-resolution megahertz X-ray photon correlation spectroscopy. This technique reveals how the proteins move within millionths of a second. “The very rapidly successive X-ray pulses from the European XFEL make it possible to observe precisely the short time scales over which proteins move in a densely packed environment,” explains Johannes Möller, a scientist at the MID instrument at the European XFEL.

The measurements show that the added molecules do not merely alter the viscosity of the solution. They also influence how the proteins arrange themselves relative to one another: Due to the presence of the molecules, the proteins attract each other and temporarily assemble into small complexes of two to three proteins. After a short time, they separate again, only to reassemble elsewhere. When bound into such complexes, the proteins move slightly slower than they do individually.

“The size and shape of the molecules that mimic the cell’s interior determine the extent to which proteins organize themselves on the smallest scale,” explains Michelle Dargasz. “In doing so, they also influence the extent to which the collective motion of the proteins is affected.”

Another finding was particularly surprising: individual proteins do not simply slow down as density increases. “Our results show that the movement of proteins does not depend solely on how viscous their environment is,” says Professor Christian Gutt of the University of Siegen, who led the study. “At low concentrations of polymer molecules, we see instead that the proteins can initially move even more freely before the damping effect of viscosity sets in—a behavior that has not been observed in this way before.”

These new findings help us better understand the processes taking place inside living cells. They provide a more realistic picture of how proteins move and interact with one another under natural conditions. In the long term, the results could help better explain fundamental biological processes—such as protein interaction or enzyme activity. Such insights could, for example, help improve drug delivery for certain diseases in the future.

Researchers from the University of Siegen, TU Dortmund, Tübingen, and Stockholm, as well as the German Electron Synchrotron (DESY) and the European XFEL, participated in the study. The research project was funded by the Federal Ministry of Research, Technology, and Space (BMFTR) as part of the ErUM-Pro program. The data processing workflow used was developed as part of the DAPHNE4NFDI initiative in accordance with the FAIR data principles.