The colloidal side of cell communication.

Up to few years ago, intercellular communication was thought to be regulated exclusively through cell-cell junctions or via exchange of soluble biomolecule messengers. However, a third way is recently strongly emerging: cells also send information by secreting micro- and nanosized extracellular vesicles (EVs), named exosomes, ectosomes and apoptotic bodies. These soft colloidal objects encode information in their content, proteins and nucleic acids, which are protected by a membranous surface tailored for long-distance circulation and cell targeting. EVs participate not only in regulation of physiological processes (such as stem cell maintenance or immune surveillance) but also in the pathology underlying several diseases [1], which fosters a wealth of therapeutic opportunities [2]. However, while bioanalytical techniques to study EV biology in-vitro and in-vivo are becoming available, knowledge on their properties at the mesoscale is very scarce. As a consequence, (nano)medical applications inherently based on surface- and nanoscience – for example as nanocargos for drugs and biologicals, therapeutic targets or means for liquid biopsy – are languishing [3]. Our contribution will present one of the first stories of integration of molecular biology with colloid chemistry in EV research. We combined the multiscale description of nanoparticle-lipid membrane interaction [4] with colloidal nanoplasmonics and the fact that nanoparticle aggregation at lipid membranes is modulated by the presence of a protein corona. This allowed us to realize a cost- effective and fast colorimetric assay for assessing by eye purity and titrate exosomes (also providing a peculiar example of nanoparticle−protein corona exploitation) [5]. This set the bases for implementing a surface plasmon resonance (SPR) biosensor to sort exosomes from Multiple Myeloma patients [6] and to assess the impact of the residual matrix from different separation techniques on the biological activity of exosome preparations [7]