Zwitterionic Dendrimersomes: A Closer Xenobiotic Mimic of Cell Membranes

Building functional mimics of cell membranes is an important task toward the development of synthetic cells. So far, lipid and amphiphilic block copolymers are the most widely used amphiphiles with the bilayers by the former lacking stability while membranes by the latter are typically characterized by very slow dynamics. Herein, a new type of Janus dendrimer containing a zwitterionic phosphocholine hydrophilic headgroup (JD(PC)) and a 3,5-substituted dihydrobenzoate-based hydrophobic dendron is introduced. JD(PC) self-assembles in water into zwitterionic dendrimersomes (z-DSs) that faithfully recapitulate the cell membrane in thickness, flexibility, and fluidity, while being resilient to harsh conditions and displaying faster pore closing dynamics in the event of membrane rupture. This enables the fabrication of hybrid DSs with components of natural membranes, including pore-forming peptides, structure-directing lipids, and glycans to create raft-like domains or onion vesicles. Moreover, z-DSs can be used to create active synthetic cells with life-like features that mimic vesicle fusion and motility as well as environmental sensing. Despite their fully synthetic nature, z-DSs are minimal cell mimics that can integrate and interact with living matter with the programmability to imitate life-like features and beyond.

Automated summary

In this study, a new type of Janus dendrimer is introduced, which can self-assemble into a mimetic cell membrane structure that closely resembles the characteristics of a natural cell membrane in terms of thickness, flexibility, and fluidity. This mimetic cell membrane exhibits resilience to harsh conditions and faster dynamics in closing pores in the event of membrane rupture. It can be used to create hybrid structures with components of natural cell membranes and has the potential to simulate life-like features such as vesicle fusion, motility, and environmental sensing.