Oral Presentation International Peptide Symposium 2023

The membrane sensing peptide toolbox in extracellular vesicles research (#72)

Alessandro Gori 1 , Marina Cretich 1 , Roberto Frigerio 1 , Paola Gagni 1 , Greta Bergamaschi 1
  1. National Research Council of Italy, Milano, LOMBARDY, Italy

Extracellular vesicles (EV) are membranous micro- and nano-sized biological particles released by cells that shuttle an impressive amount of molecular information, thus representing a phenomenal source of biomarkers. To date, the highest clinical relevance is believed to reside in small EVs (sEV), including exosomes, which are generating unparalleled expectations as the next generation theragnostic tools. Here, we report on the use of membrane curvature sensing peptides (MSP) as a new class of molecular ligands for EV. The EV membrane, given its characteristic high curvature, can in fact be considered as a ‘universal’ marker of EVs, oppositely to surface-associated proteins, which suffer instead from remarkable abundance heterogeneity . As such, the use of MSP ligands for the multipurpose and unbiased EVs isolation shows considerable advantages over the traditional use of antibodies, as demonstrated here by their direct integration onto advanced microanalytic platforms for liquid biopsy applications, including microarrays, a single-particle interferometric reflectance imaging sensor, and a bead-supported single-molecule detection immunosandwich assays. Overall, we introduce the first demonstration of the use of MSP as molecular baits for the isolation and analysis of extracellular vesicles. We anticipate that this new class of ligands, also due to the versatility of synthetic peptides, may greatly enrich the molecular toolbox for EV research, and further perspectives beyond analytics will be discussed.

  1. A. Gori* et al., J. Extr. Ves. (2020), 9:1, 1751428, DOI: 10.1080/20013078.2020.1751428