Dendritic Membranized Coacervate Microdroplets: A Robust Platform for Synthetic-Living Cell Consortia

Abstract

Bottom-up synthetic biology seeks to construct artificial cells with biomimetic or novel functionalities to uncover the fundamental principles of cellular evolution and drive advances in medicine and bioengineering. Among them, membranized coacervate microdroplets (MCM) uniquely combine a molecularly crowded aqueous interior with a surrounding membrane, both hallmarks of eukaryotic cells. Replicating cellular functions requires synthetic cells to remain structurally stable in biological environments, where ionic strength presents a significant threat to the integrity of complex coacervates. By leveraging the globular and rigid architecture of dendrimers, MCM, composed of oppositely charged small dendrimers and polypeptides─further stabilized by a charged PEG-dendritic copolymer assembled at the periphery─exhibits a critical salt concentration more than twice that of coacervates formed from polypeptides or branched polyelectrolytes with significantly higher degrees of polymerization. This highlights the enhanced robustness of dendritic MCM under physiological conditions and their suitability as synthetic cells in biological media. By mimicking key cell-like behavior such as efficient enzyme encapsulation (irrespective of the isoelectric point), fast internal dynamics, and chemical communication, dendritic MCM emerge as a promising synthetic cell platform for the selective delivery of therapeutic enzymes. In addition, their ability to engage in signal transduction pathways within synthetic-natural cell consortia, enabling responses to extracellular cues via chemical signaling, paves their way in tissue engineering and regenerative medicine.