AlbaNova and Nordita colloquium

When Diffusion Slows Down: How Crowding, Hydrodynamics, and Softness Shape Protein Motion

Prof. Christian Gutt (Universität Siegen)

7 May 2026, 15:15 - The Oskar Klein auditorium (FR4)

Biological environments are highly crowded, with macromolecular volume fractions often exceeding 30–40%. In such conditions, protein motion deviates strongly from simple Brownian diffusion, yet the physical mechanisms governing this behavior remain poorly understood due to a long-standing experimental gap at nanometer length scales and microsecond times. In this talk, I will present recent advances using megahertz X-ray photon correlation spectroscopy (MHz-XPCS) at X-ray free-electron lasers to directly probe protein dynamics in this previously inaccessible regime. These measurements reveal that protein motion in crowded environments is governed by a complex interplay of transient caging, hydrodynamic interactions, and particle softness, leading to anomalous, non-exponential relaxation dynamics. Across model systems ranging from globular proteins in polymeric crowders to native lipoproteins in dense biological fluids, we observe a strong coupling between structure and dynamics, including collective slowing-down at characteristic length scales and pronounced deviations from classical diffusion–viscosity relations.

Together, these results establish a physical picture in which protein transport is controlled not only by excluded volume, but by interaction-specific effects and many-body hydrodynamics. This framework provides new insight into molecular motion in biological media and has implications for processes ranging from intracellular transport to drug delivery in complex fluids.