Lipoprotein diffusion in dense yolk plasma is governed by softness, hydrodynamics, and caging: Insights from MHz-XPCS

N Nimmi Das Anthuparambil (Department Physik, Universität Siegen) M Michelle Dargasz (Department Physik, Universität Siegen) S Sonja Timmermann (Department Physik, Universität Siegen) A Anita Girelli (Department of Physics, AlbaNova University Center, Stockholm University) S Sebastian Retzbach (Institut für Angewandte Physik, Universität Tübingen) J Johannes Möller (European X-Ray Free-Electron Laser Facility) W Wonhyuk Jo (European X-Ray Free-Electron Laser Facility) A Agha Mohammad Raza (Department Physik) A Aliaksandr Leonau (Department Physik, Universität Siegen) J James Wrigley (European X-Ray Free-Electron Laser Facility) F Frederik Unger (Department Physik, Universität Siegen) M Maddalena Bin (Department of Physics, AlbaNova University Center, Stockholm University) P Prince Prabhu Rajaiah (Institute for Biochemistry and Molecular Biology) I Iason Andronis (Department of Physics, AlbaNova University Center, Stockholm University) W William Chèvremont (The European Synchrotron, ESRF, 71 Avenue des Martyrs, CS40220, Grenoble 38043, France) J Jörg Hallmann (European X-Ray Free-Electron Laser Facility) A Angel Rodriguez-Fernandez (European X-Ray Free-Electron Laser Facility) J Jan-Etienne Pudell (European X-Ray Free-Electron Laser Facility) F Felix Brausse (European X-Ray Free-Electron Laser Facility) U Ulrike Boesenberg (European X-Ray Free-Electron Laser Facility) M Mohamed Youssef (European X-Ray Free-Electron Laser Facility) R Roman Shayduk (European X-Ray Free-Electron Laser Facility) R Rustam Rysov (European X-Ray Free-Electron Laser Facility) A Anders Madsen (European X-Ray Free-Electron Laser Facility) F Felix Lehmkühler (Deutsches Elektronen-Synchrotron) M Michael Paulus (Fakultät Physik/DELTA) F Fajun Zhang (Institut für Angewandte Physik, Universität Tübingen) F Fivos Perakis (Department of Physics, AlbaNova University Center, Stockholm University) F Frank Schreiber (Institut für Angewandte Physik, Universität Tübingen) C Christian Gutt (Department Physik, Universität Siegen)

Abstract

Low-density lipoproteins (LDLs) are central to nutrient transport in egg yolk and have emerged as natural nanocarriers for drug delivery. Their biological function critically depends on mobility within densely crowded environments, yet the mechanisms governing their motion remain elusive, largely because conventional techniques cannot access the relevant microsecond timescales. Here, we employ megahertz X-ray photon correlation spectroscopy at the European X-ray Free Electron Laser facility to resolve LDL dynamics in native yolk-plasma. This approach reveals transient caging and memory effects and shows that the combined influence of particle softness and hydrodynamic coupling slows diffusion by nearly two orders of magnitude compared to dilute solutions. However, this reduction could not be scaled with an increase in macroscopic viscosity obtained from rheometry, indicating deviations from the Stokes–Einstein relation. Despite this slowdown, yolk-plasma remains a “sluggish yet liquid state”, balancing dense packing and the fluidity required for lipid release during embryonic development. These results establish a quantitative framework connecting microstructure, hydrodynamics, and transport in crowded soft-matter systems, with implications for developmental biology and nanomedicine.

Article Details

Volume / Issue Vol. 123, Issue 8
Published February 24, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (30)

N

Nimmi Das Anthuparambil

Department Physik, Universität Siegen

M

Michelle Dargasz

Department Physik, Universität Siegen

S

Sonja Timmermann

Department Physik, Universität Siegen

A

Anita Girelli

Department of Physics, AlbaNova University Center, Stockholm University

S

Sebastian Retzbach

Institut für Angewandte Physik, Universität Tübingen

J

Johannes Möller

European X-Ray Free-Electron Laser Facility

W

Wonhyuk Jo

European X-Ray Free-Electron Laser Facility

A

Agha Mohammad Raza

Department Physik

A

Aliaksandr Leonau

Department Physik, Universität Siegen

J

James Wrigley

European X-Ray Free-Electron Laser Facility

F

Frederik Unger

Department Physik, Universität Siegen

M

Maddalena Bin

Department of Physics, AlbaNova University Center, Stockholm University

P

Prince Prabhu Rajaiah

Institute for Biochemistry and Molecular Biology

I

Iason Andronis

Department of Physics, AlbaNova University Center, Stockholm University

W

William Chèvremont

The European Synchrotron, ESRF, 71 Avenue des Martyrs, CS40220, Grenoble 38043, France

J

Jörg Hallmann

European X-Ray Free-Electron Laser Facility

A

Angel Rodriguez-Fernandez

European X-Ray Free-Electron Laser Facility

J

Jan-Etienne Pudell

European X-Ray Free-Electron Laser Facility

F

Felix Brausse

European X-Ray Free-Electron Laser Facility

U

Ulrike Boesenberg

European X-Ray Free-Electron Laser Facility

M

Mohamed Youssef

European X-Ray Free-Electron Laser Facility

R

Roman Shayduk

European X-Ray Free-Electron Laser Facility

R

Rustam Rysov

European X-Ray Free-Electron Laser Facility

A

Anders Madsen

European X-Ray Free-Electron Laser Facility

F

Felix Lehmkühler

Deutsches Elektronen-Synchrotron

M

Michael Paulus

Fakultät Physik/DELTA

F

Fajun Zhang

Institut für Angewandte Physik, Universität Tübingen

F

Fivos Perakis

Department of Physics, AlbaNova University Center, Stockholm University

F

Frank Schreiber

Institut für Angewandte Physik, Universität Tübingen

C

Christian Gutt

Department Physik, Universität Siegen