Orthogonal Investigation at Single-Particle and Ensemble Levels Uncovers Lipoprotein-Extracellular Vesicle Binding
Angelo Musicò, Roberto Frigerio, Karl Normak, Sabrina Scolari, Alessandro Gori, Paolo Arosio, Annalisa Radeghieri, Lucia Paolini, Miriam Romano, Irantzu Llarena, Sergio E. Moya, Andrea Zendrini, Paolo Bergese

TL;DR
The study explores how extracellular vesicles from red blood cells interact with lipoproteins in different environments, revealing complex and dynamic binding patterns.
Contribution
The work introduces a novel methodological framework using multiple analytical techniques to study extracellular vesicle-lipoprotein interactions at various scales.
Findings
Lipoproteins bind to extracellular vesicles with affinities ranging from 10 nM to 1 μM.
Up to 100% of extracellular vesicles interact with high-density lipoproteins in plasma conditions.
The study reveals class-specific and context-dependent associations between extracellular vesicles and lipoproteins.
Abstract
Mesoscale interactions critically shape the biological identity of extracellular nanoparticles, including extracellular vesicles. These interactions encompass biomolecular coronas, transient aggregation, and fusion events. Among them, the interaction between extracellular vesicles and lipoproteins has recently garnered significant attention due to their potential impact on functionality and in vivo fate of extracellular vesicles. In this work, we present a first investigation of the binding between human red blood cell-derived extracellular vesicles and lipoproteins across multiple scales, in both buffer and plasma. Red blood cell-derived extracellular vesicles were selected as a model system for their physicochemical homogeneity, potential in personalized medicine, and production scalability. To achieve this, we employed an ad hoc suite of orthogonal analytical techniques: fluorescence…
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Taxonomy
TopicsExtracellular vesicles in disease · Erythrocyte Function and Pathophysiology · Neutrophil, Myeloperoxidase and Oxidative Mechanisms
