LAUSR

Significance Lipid vesicles are globular assemblies that compartmentalize, encapsulate, transport, and provide signal transmission and communication between cells. In living systems, these vesicles perform critical functions to sustain life. Biomimetic lipid vesicles, such as liposomes, have been developed as mimics of biological cell membranes and for applications in biotechnology, but they do have specific limitations. Dendrimersomes are vesicles self-assembled from amphiphilic Janus dendrimers. They offer improved stability and versatility over liposomes. These dendrimersomes are extremely efficient at loading hydrophobic small molecules and natural macromolecules including folded proteins, at a level higher than comparable liposomes. Additionally, they can be readily functionalized to enable modular recruitment of proteins and nucleic acids on their periphery. Reconstructing the functions of living cells using nonnatural components is one of the great challenges of natural sciences. Compartmentalization, encapsulation, and surface decoration of globular assemblies, known as vesicles, represent key early steps in the reconstitution of synthetic cells. Here we report that vesicles self-assembled from amphiphilic Janus dendrimers, called dendrimersomes, encapsulate high concentrations of hydrophobic components and do so more efficiently than commercially available stealth liposomes assembled from phospholipid components. Multilayer onion-like dendrimersomes demonstrate a particularly high capacity for loading low-molecular weight compounds and even folded proteins. Coassembly of amphiphilic Janus dendrimers with metal-chelating ligands conjugated to amphiphilic Janus dendrimers generates dendrimersomes that selectively display folded proteins on their periphery in an oriented manner. A modular strategy for tethering nucleic acids to the surface of dendrimersomes is also demonstrated. These findings augment the functional capabilities of dendrimersomes to serve as versatile biological membrane mimics.