A multifarious platform for Extracellular Vesicles analysis

Extracellular Vesicles (EV) are biogenic nanoparticles released by almost any cell and carry a variety of proteins, lipids, and nucleic acids. By transferring these biomolecules, EVs play important roles in intercellular communication, as such they are gaining increasing importance as potential biomarkers and therapeutic agents. This exciting area of research face big challenges due to EV small size, low refractive index, inherent heterogeneity, and high sensitivity demand in detecting low abundant disease-specific sub-populations. Such need can be met by innovative affinity-probes and digital detection, namely capable to reach the single-molecule sensitivity. Our recent work has identified a class of membrane-sensing peptides (MSP) derived from Bradykinin protein as a novel class of molecular ligands for integrated small EV isolation and analysis. The membrane recognition and binding mechanisms are based on complementary electrostatic interactions between peptide and phospholipids on the outer membrane leaflet, that subsequently can lead to the insertion of hydrophobic residues into the membrane defects. Notably, small EVs present distinctive lipid membrane features in the extracellular environment that could be considered as a universal marker, alternative or complementary to traditional characteristic surface-associated proteins. MSPs are therefore pan-specific, interspecies and interkingdom thus representing a multifarious class of ligands with additional advantages in terms of stability and synthetic versatility.