SmallTalks: The sugar-coated truth – Nanofluidic insights into extracellular vesicle surface charge

Abstract 

Extracellular Vesicles (EVs) are biological nanoparticles released by cells to mediate cell-to-cell communication. Beyond their essential roles in normal physiology, EVs have also been implicated in several pathological processes.

Despite its likely influence on both short range EV-cell interactions and long-range electrostatic interactions within the extracellular environment, EV surface charge remains poorly understood. However, a key contributor is thought to be the decoration of certain sugar molecules (glycans) on the surface.

Here, we utilize a nanofluidic device coupled with fluorescence microscopy for high-throughput, single-particle analysis of EV size, biomolecular content and surface charge within a single measurement. By applying an electrical field across the nanochannels we simultaneously track electrophoretic mobility and Brownian motion of individual particles, revealing distinct charge–size relationships across EV subpopulations.

Using this platform, we investigate the interplay between surface glycans and EV charge, highlighting surface charge as an important, yet underexplored dimension of EV heterogeneity.