From Nano to Micro Polyion Complex Vesicles: Synthetic Cells with Membrane-Embedded Enzymes

Synthetic cells are emerging as cornerstone in our understanding of prebiotic forms of early life and the development of therapeutics. Although several types of vesicles have been proposed for this purpose, their development is often hampered by limited membrane permeability. On the other hand, polyion complex vesicles (PICsomes) with a high permeability for small molecules suffer from a small size (typically sub-200 nm) and low encapsulation efficiency of enzymes (less than 4%). Herein, we describe the peripheral charge density of dendrimers and the ionic strength of the medium as powerful tools in the size tuning of PICsomes via a dendrimer-to-PIC hierarchical transfer of structural information. PICsomes beyond the micron range were readily obtained from a single dendrimer generation (G) and their ability to emulate life-like technologies explored through chemical communication. As opposed to the low protein encapsulation in the lumen of classical PICsomes, a selective enzyme embedding in the PIC membrane was revealed with efficiencies up to 85%. Notably, membrane-embedded enzymes retain high catalytic activity (85% relative to free enzymes), even in the presence of proteases, enabling fast enzymatic cascades between synthetic cell populations.