Coherent X-rays reveal anomalous molecular diffusion and cage effects in crowded protein solutions

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<sub>2</sub>(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 δγ-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.

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Publication Details

Journal
Nature Communications
Published
2025-11-29
DOI
https://doi.org/10.1038/s41467-025-66972-6
Citations
2
Primary Topic
Spectroscopy and Quantum Chemical Studies
Type
article
Field-Weighted Citation Impact
2.49

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article

Coherent X-rays reveal anomalous molecular diffusion and cage effects in crowded protein solutions

William Chèvremont, Frank Schreiber, Iason Andronis, Ulrike Boesenberg et al.
2 citations
Nature Communications
Spectroscopy and Quantum Chemical Studies
2.49
article

Coherent X-rays reveal anomalous molecular diffusion and cage effects in crowded protein solutions

William Chèvremont, Frank Schreiber, Iason Andronis, Ulrike Boesenberg, Prabhu Rajaiah Prince, Wonhyuk Jo, Sonja Timmermann, Jörg Hallmann, Roman Shayduk, Nimmi Das Anthuparambil, James J. Wrigley, Mario Reiser, Anders Madsen, Jan‐Etienne Pudell, Johannes Möller, Wei Lu, Mohammad Sayed Akhundzadeh, Maddalena Bin, Marvin Kowalski, Alexey V. Zozulya, Angel Rodríguez-Fernández, Michael Paulus, Tilo Seydel, Trey Guest, Asaf Raza, Felix Brauße, Sebastian Retzbach, Lara Franziska Reichart, Christian Gutt, Mariia Filianina, Sharon Berkowicz, Felix Lehmkühler, Michelle Dargasz, Fajun Zhang, Maximilian D. Senft, Fivos Perakis, Anita Girelli, C. H. Woo, Jenny Schrage, Aliaksandr Leonau
article en
2 citations

Abstract

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<sub>2</sub>(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 δγ-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.

Nature CommunicationsVol. 16(1)
Universität Hamburg (DE), Stockholm University (SE), TU Dortmund University (DE), University of Siegen (DE), Folkwang University of the Arts (DE), Deutsches Elektronen-Synchrotron DESY (DE), European Synchrotron Radiation Facility (FR), Institut Laue-Langevin (FR), AlbaNova (SE), Max Planck Institute for the Structure and Dynamics of Matter (DE), Centre for Structural Systems Biology (DE), Hamburg Centre for Ultrafast Imaging, University of Tübingen (DE), European X-Ray Free-Electron Laser (DE)
Wenner-Gren Stiftelserna, European Commission, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, European Synchrotron Radiation Facility, Bundesministerium für Bildung und Forschung, Max-Planck-Gesellschaft, Vetenskapsrådet, Stockholms Universitet, HORIZON EUROPE Framework Programme, Deutsches Elektronen-Synchrotron
Openalex Percentile: Top 9%
Spectroscopy and Quantum Chemical Studies
2.49
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