RT Journal Article T1 From Nano to Micro Polyion Complex Vesicles: Synthetic Cells with Membrane-Embedded Enzymes A1 Jiménez López, Celia A1 López-Blanco, Roi A1 Esperón Abril, Iria A1 Fernández Megía, Eduardo K1 Dendrimer K1 Polyion complex vesicle K1 PICsome K1 Synthetic cell K1 Hierarchical transfer AB 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. PB ACS SN 1944-8244 YR 2025 FD 2025-08-10 LK https://hdl.handle.net/10347/43060 UL https://hdl.handle.net/10347/43060 LA eng NO Jimenez-Lopez, C., Lopez-Blanco, R., Esperon-Abril, I., and Fernandez-Megia, E. (2025). From nano to micro polyion complex vesicles: Synthetic cells with membrane-embedded enzymes. “ACS Applied Materials & Interfaces”, Vol. 17 (33), 47426-47435. DOI: 10.1021/acsami.5c11988 NO This work was supported by grants PID2021-127684OB-I00 and PID2024-162826OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF “A way of making Europe”. The authors also thank financial support from Xunta de Galicia (ED431C 2022/21, and Centro de Investigación do Sistema Universitario de Galicia accreditation 2023-2027, ED431G 2023/03) and the European Union (European Regional Development Fund - ERDF). The authors are grateful to Carlos Fernández Pereira for helpful discussions about the fitting of PIC size data to eqs 1–4. The authors thank María Teresa Bueno, Francisco Javier Chichón, and Rocío Arranz for cryo-TEM data collection at the CryoEM Facility of Centro Nacional de Biotecnología-CSIC (Madrid, Spain). DS Minerva RD 28 abr 2026