Coherent X-rays reveal anomalous molecular diffusion and cage effects in crowded protein solutions
Abstract
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 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.
Article Details
Authors (41)
Anita Girelli
Department of Physics, AlbaNova University Center, Stockholm University
Maddalena Bin
Department of Physics, AlbaNova University Center, Stockholm University
Mariia Filianina
Michelle Dargasz
Department Physik, Universität Siegen
Nimmi Das Anthuparambil
Department Physik, Universität Siegen
Johannes Möller
European X-Ray Free-Electron Laser Facility
Alexey Zozulya
European X-Ray Free-Electron Laser Facility
Iason Andronis
Department of Physics, AlbaNova University Center, Stockholm University
Sonja Timmermann
Department Physik, Universität Siegen
Sharon Berkowicz
Sebastian Retzbach
Institut für Angewandte Physik, Universität Tübingen
Mario Reiser
Agha Mohammad Raza
Department Physik
Marvin Kowalski
Mohammad Sayed Akhundzadeh
Jenny Schrage
Chang Hee Woo
Maximilian D. Senft
Institut für Angewandte Physik, Universität Tübingen 3 , 72076 Tübingen,
Lara Franziska Reichart
Aliaksandr Leonau
Department Physik, Universität Siegen
Prabhu Rajaiah Prince
William Chèvremont
The European Synchrotron, ESRF, 71 Avenue des Martyrs, CS40220, Grenoble 38043, France
Tilo Seydel
Institut Max von Laue – Paul Langevin
Jörg Hallmann
European X-Ray Free-Electron Laser Facility
Angel Rodriguez-Fernandez
European X-Ray Free-Electron Laser Facility
Jan-Etienne Pudell
European X-Ray Free-Electron Laser Facility
Felix Brausse
European X-Ray Free-Electron Laser Facility
Ulrike Boesenberg
European X-Ray Free-Electron Laser Facility
James Wrigley
European X-Ray Free-Electron Laser Facility
Mohamed Youssef
European X-Ray Free-Electron Laser Facility
Wei Lu
Wonhyuk Jo
European X-Ray Free-Electron Laser Facility
Roman Shayduk
European X-Ray Free-Electron Laser Facility
Trey Guest
Anders Madsen
European X-Ray Free-Electron Laser Facility
Felix Lehmkühler
Deutsches Elektronen-Synchrotron
Michael Paulus
Fakultät Physik/DELTA
Fajun Zhang
Institut für Angewandte Physik, Universität Tübingen
Frank Schreiber
Institut für Angewandte Physik, Universität Tübingen
Christian Gutt
Department Physik, Universität Siegen
Fivos Perakis
Department of Physics, AlbaNova University Center, Stockholm University