SNARE‐Reconstituted Liposomes as Controllable Zeptoliter Nanoreactors for Macromolecules

Liposomes are synthetic phospholipid vesicles containing an aqueous lumen confined by a lipid bilayer. These vesicles have been used as nanoreactors because they offer confined environments that can result in significant changes to chemistry. However, a major limitation of using liposomes as nanocontainers is the impermeability of their lipid membranes. To overcome this, scientists have tested the use of porous liposomes generated by membrane phase changes or by pore formation proteins. In this study, the selective permeability of porous liposomes to molecules smaller than the threshold pore size is demonstrated for triggering internal reactions. Furthermore, in order to deliver macromolecules larger than the threshold pore size into lipid-based nanoreactors, fusogenic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins were employed to mediate membrane fusion between two liposomes to initiate reactions on demand without losing previously encapsulated macromolecules. This novel approach circumvents limitations associated with inserting molecules larger than the threshold pore size of porous lipid membranes.