Orthogonal Investigation at Single-Particle and Ensemble Levels Uncovers Lipoprotein-Extracellular Vesicle Binding.
Angelo Musicò1,2, Roberto Frigerio1,2,3, Karl Normak3
1Department of Molecular and Translational Medicine (DMMT), University of Brescia, 25123 Brescia, Italy.
Analytical Chemistry
|January 8, 2026
Summary
Extracellular vesicles (EVs) interact with lipoproteins, influencing their function. This study reveals specific, context-dependent binding affinities between red blood cell-derived EVs and lipoproteins in plasma.
Area of Science:
- Biophysics
- Nanomedicine
- Biochemistry
Background:
- Mesoscale interactions, including biomolecular coronas, aggregation, and fusion, define nanoparticle identity.
- Extracellular vesicle (EV)-lipoprotein interactions are crucial for EV functionality and in vivo behavior.
- Understanding these interactions is vital for applications in personalized medicine.
Purpose of the Study:
- To investigate the binding of human red blood cell-derived EVs with lipoproteins.
- To analyze these interactions across multiple scales and in different environments (buffer and plasma).
- To establish a methodological framework for studying nanoparticle-lipoprotein interactions.
Main Methods:
- Utilized fluorescence cross-correlation spectroscopy (FCCS).
- Employed super-resolution microscopy.
- Applied flow cytometry and Single Molecule Array (Simoa) assays.
Main Results:
- Demonstrated class-specific and context-dependent EV-lipoprotein associations.
- Quantified binding affinities between 10 nM and 1 μM.
- Observed up to 100% EV interaction with high-density lipoproteins in plasma.
Conclusions:
- Uncovered a complex and dynamic interactome between red blood cell-derived EVs and lipoproteins.
- Established a robust framework for studying mesoscale interactions of extracellular nanoparticles.
- Highlighted the importance of context-dependent effects on EV-lipoprotein binding.
