Journal Article

PUBDB-2025-01947

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Depletion-induced interactions modulate nanoscale protein diffusion in polymeric crowder solutions

Dargasz, M. (Corresponding author)Extern*XFEL.EU* ; Anthuparambil, N. D.Extern* ; Retzbach, S.Extern* ; Girelli, A.Extern*XFEL.EU* ; Timmermann, J.Extern* ; Moeller, J.XFEL.EU* ; Jo, W.Extern* ; Leonau, A.XFEL.EU* ; Raza Agha, M. ; Bin, M.Extern*XFEL.EU* ; Savelkouls, J.Extern* ; Andronis, I.Extern*XFEL.EU* ; Unger, F.Extern* ; Brausse, F.Extern*XFEL.EU*DESY* ; Hallmann, J.XFEL.EU* ; Boesenberg, U.XFEL.EU* ; Pudell, J.-E.XFEL.EU* ; Rodriguez-Fernandez, A.Extern*XFEL.EU* ; Wrigley, J.XFEL.EU* ; Shayduk, R.XFEL.EU* ; Youssef, M. H.Extern*XFEL.EU*DESY* ; Zozulya, A.XFEL.EU* ; Madsen, A.XFEL.EU* ; Lehmkühler, F.XFEL.EU*DESY* ; Perakis, F.Extern* ; Zhang, F.Extern* ; Schreiber, F.Extern* ; Paulus, M.Extern* ; Gutt, C.Extern*XFEL.EU*

2026
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.2524733123  doi:10.3204/PUBDB-2025-01947

Abstract: Macromolecular crowding plays a crucial role in modulating protein dynamics in cellular and in vitro environments. Polymeric crowders such as dextran and Ficoll are known to induce entropic forces, including depletion interactions, that promote structural organization, yet their nanoscale consequences for protein dynamics remain poorly understood. Here, we employ megahertz X-ray photon correlation spectroscopy (MHz-XPCS) at the European X-ray Free Electron Laser (XFEL) to probe the dynamics of the protein ferritin in solutions containing sucrose, dextran, and Ficoll. We find pronounced changes in collective protein dynamics in polymeric crowders, revealing depletion-driven short-range attractions that, combined with long-range repulsions, give rise to intermediate-range organization. These mesoscale correlations undergo collective relaxation on microsecond to millisecond timescales, as directly resolved by XPCS through the decay of ferritin density fluctuations. The magnitude of this depends sensitively on crowder molecular weight and type. Normalizing the crowder concentration by c* reveals scaling behavior of ferritin self-diffusion with a crossover near 2c*, marking a transition from depletion-enhanced mobility to viscosity-dominated slowing. Our results demonstrate that bulk properties alone are insufficient to describe protein dynamics in crowded solutions, highlighting the need to include polymer-specific interactions and depletion theory in models of crowded environments.

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Contributing Institute(s):

1. Spectroscopy of molecular processes (FS-SMP)
2. Coherent X-ray Scattering (FS-CXS)
3. MID (XFEL_E1_MID)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)
2. DFG project G:(GEPRIS)460248799 - DAPHNE4NFDI - DAten aus PHoton- und Neutronen Experimenten für NFDI (460248799) (460248799)
3. PRISMAS - PhD Research and Innovation in Synchrotron Methods and Applications in Sweden (101081419) (101081419)

Experiment(s):

1. MID: Materials Imaging and Dynamics (SASE2)
2. XFEL Beamline SASE 2 (XFEL)

Appears in the scientific report 2026

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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