Coherent X-rays reveal anomalous molecular diffusion and cage effects in crowded protein solutions
/ Authors
A. Girelli, Maddalena Bin, Mariia Filianina, M. Dargasz, Nimmi Das Anthuparambil, J. Möller, A. Zozulya, I. Andronis, Sonja Timmermann, Sharon Berkowicz
and 31 more authors
Sebastian Retzbach, M. Reiser, A. Raza, Marvin Kowalski, Mohammad Sayed Akhundzadeh, Jenny Schrage, Chang Hee Woo, Maximilian D. Senft, L. F. Reichart, A. Leonau, P. R. Prince, W. Chèvremont, T. Seydel, Joerg Hallmann, A. Rodriguez-Fernandez, Jan-Etienne Pudell, Felix Brausse, U. Boesenberg, James Wrigley, M. Youssef, Wei Lu, Wonhyuk Jo, R. Shayduk, Trey Guest, A. Madsen, F. Lehmkühler, Michael Paulus, Fajun Zhang, Frank Schreiber, C. Gutt, F. Perakis
/ 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 g2(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. Protein motion in crowded environments governs cellular transport and reaction rates. Here, the authors use megahertz X-ray Photon Correlation Spectroscopy to reveal anomalous diffusion of ferritin, linking hydrodynamic and direct interactions to cage-trapping at microsecond time scales.
Journal: Nature Communications