Coherent X-rays reveal anomalous molecular diffusion and cage effects in crowded protein solutions
- Anita Girelli
- Maddalena Bin
- Mariia Filianina
- Michelle Dargasz
- Nimmi Das Anthuparambil
- Johannes Möller
- Alexey Zozulya
- Iason Andronis
- Sonja Timmermann
- Sharon Berkowicz
- Sebastian Retzbach
- Mario Reiser
- Agha Mohammad Raza
- Marvin Kowalski
- Mohammad Sayed Akhundzadeh
- Jenny Schrage
- Chang Hee Woo
- Maximilian D. Senft
- Lara Franziska Reichart
- Aliaksandr Leonau
- Prabhu Rajaiah Prince
- William Chèvremont
- Tilo Seydel
- Jörg Hallmann
- Angel Rodriguez-Fernandez
- Jan-Etienne Pudell
- Felix Brausse
- Ulrike Boesenberg
- James Wrigley
- Mohamed Youssef
- Wei Lu
- Wonhyuk Jo
- Roman Shayduk
- Trey Guest
- Anders Madsen
- Felix Lehmkühler
- Michael Paulus
- Fajun Zhang
- Frank Schreiber
- Christian Gutt
- Fivos Perakis
2025-11-29
Understanding protein motion within the cell is crucial for predicting reaction rates and macromolecular transport in the cytoplasm. A key question is how crowded environments affect protein dynamics through hydrodynamic and direct interactions at molecular length scales. Using megahertz X-ray Photon Correlation Spectroscopy (MHz-XPCS) at the European X-ray Free Electron Laser (EuXFEL), we investigate ferritin diffusion at microsecond time scales. Our results reveal anomalous diffusion, indicated by the non-exponential decay of the intensity autocorrelation function g 2 ( q , t ) at high concentrations. This behavior is consistent with the presence of cage-trapping between the short- and long-time protein diffusion regimes. Modeling with the δ γ -theory of hydrodynamically interacting colloidal spheres successfully reproduces the experimental data by including a scaling factor linked to the protein direct interactions. These findings offer insights into the complex molecular motion in crowded protein solutions, with potential applications for optimizing ferritin-based drug delivery, where protein diffusion is the rate-limiting step.