Structural insights into fusion mechanisms of small extracellular vesicles with model plasma membranes

Fabio Perissinotto, Valeria Rondelli, Beatrice Sinigaliesi, Paola Brocca, Lazlo Almasy, Lazlo Bottyan, Daniel Geza Merkel, Heinz Amenitsch, Barbara Sartori, Karin Pachler, Magdalena Mayr, Mario Gimona, Eva Rhode, Loredana Casalis*, Pietro Parisse*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Extracellular vesicles (EVs) are a potent intercellular communication system. Such small vesicles transport biomolecules between cells and throughout the body, strongly influencing the fate of recipient cells. Due to their specific biological functions they have been proposed as biomarkers for various diseases and as optimal candidates for therapeutic applications. Despite their extreme biological relevance, their mechanisms of interaction with the membranes of recipient cells are still hotly debated. Here, we propose a multiscale investigation based on atomic force microscopy, small angle X-ray scattering, small angle neutron scattering and neutron reflectometry to reveal structure-function correlations of purified EVs in interaction with model membrane systems of variable complex compositions and to spot the role of different membrane phases on the vesicle internalization routes. Our analysis reveals strong interactions of EVs with the model membranes and preferentially with the borders of protruding phase domains. Moreover, we found that upon vesicle breaking on the model membrane surface, the biomolecules carried by/on EVs diffuse with different kinetics rates, in a process distinct from simple fusion. The biophysical platform proposed here has clear implications on the modulation of EV internalization routes by targeting specific domains at the plasma cell membrane and, as a consequence, on EV-based therapies. This journal is

Original languageEnglish
Pages (from-to)5224-5233
Number of pages10
Issue number10
Publication statusPublished - 2021

ASJC Scopus subject areas

  • Biophysics

Fields of Expertise

  • Advanced Materials Science


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