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Exosome‐associated polysialic acid modulates membrane potentials, membrane thermotropic properties, and raft‐dependent interactions between vesicles

In mammals, polysialic acid (polySia) attached to a small number of transmembrane protein carriers occurs on the surface of plasma membranes of neural, cancer, immune, and placental trophoblast cells. Here, our goal was to demonstrate the presence of polySia on exosomes and its effect on membrane properties. We isolated exosomes and found that polysialylated exosomes in fetal bovine serum originate mostly from placental trophoblasts, while in calf bovine serum, they originate from immune cells. Enzymatic removal of polySia chains from the exosomal surface makes the membrane surface potential more positive, transmembrane potential more negative, and reduces the activation energy for membrane anisotropy changes. We demonstrate for the first time that exosomes could interact through polySia–raft interactions. We suggest that polysialylation of exosomal membrane can have a thermo‐protecting effect and can modulate exosome–plasma membrane interactions.