Extracellular vesicle surface interactome (EV surface interactome)

The extracellular vesicle (EV) surface interactome represents the collective assembly of proteins, lipids, glycans, and nucleic acids present on the exterior of EVs, including exosomes and microvesicles [1, 2]. This interactome serves as the primary interface for intercellular communication, where surface molecules act as molecular addresses that dictate the targeting and uptake of EVs by specific recipient cells [4, 6]. Key components include tetraspanins (such as CD63, CD9, and CD81), integrins, and various receptors that facilitate docking, adhesion, and signal transduction [1, 4]. In pathological conditions, the EV surface interactome is often hijacked; for instance, cancer-derived EVs use specific surface proteins to prepare pre-metastatic niches or transfer oncogenic receptors like EGFRvIII to neighboring cells [6, 14]. Therapeutically, this interactome is targeted through the use of antibodies or peptides to block disease-promoting interactions or by engineering EVs to display specific ligands for targeted drug delivery [12, 13]. Despite its potential, the high heterogeneity of EV populations and the ubiquitous expression of many surface markers present significant challenges for clinical translation [10, 14].

Other names

EV surfaceomeExosome surface interactomeExtracellular vesicle surface proteinsEV surface molecular network

Modulation of intercellular communication by blocking specific EV-cell surface interactions, facilitating immunoisolation for diagnostic profiling, or utilizing engineered surface ligands to achieve cell-specific delivery of therapeutic cargoes [2, 12, 13].