Electrostatic interactions control the adsorption of extracellular vesicles onto supported lipid bilayers

Communication between cells located in different parts of an organism is often mediated by membrane-enveloped nanoparticles, such as extracellular vesicles (EVs). EV binding and cell uptake mechanisms depend on the heterogeneous composition of the EV membrane. From a colloidal perspective, the EV membrane interacts with other biological interfaces via both specific and non-specific interactions, where the latter include long-ranged electrostatic and van der Waals forces, and short-ranged repulsive "steric-hydration" forces. While electrostatic forces are generally exploited in most EV immobilization protocols, the roles played by various colloidal forces in controlling EV adsorption on surfaces have not yet been thoroughly addressed. In the present work, we study the interaction and adsorption of EVs with supported lipid bilayers (SLBs) carrying different surface charge densities. By probing the EV-SLB interaction using quartz crystal microbalance with dissipation monitoring (QCM-D) and confocal laser scanning microscopy (CLSM), we demonstrate that EV adsorption onto lipid membranes can be controlled by varying the strength of electrostatic forces. We then model the observed phenomena within the framework of nonlinear Poisson-Boltzmann theory. Modelling results confirm the experimental observations and highlight the crucial role played by attractive electrostatics in EV adsorption onto lipid membranes. Our results provide new fundamental insights into EV-membrane interactions and could be useful for developing novel EV separation and immobilization strategies.