Monodisperse Giant Unilamellar Niosomes as Minimal Synthetic Cells

Giant unilamellar vesicles (GUVs) such as liposomes, polymersomes, and fatty acid vesicles are widely studied as synthetic cell models. However, liposomes suffer from limited membrane permeability, instability, and high material cost, while polymersomes lack membrane fluidity, and fatty acid vesicles are sensitive to ions and pH. Here, we introduce giant unilamellar niosomes (GUNs), nonionic surfactant-based vesicles, as a robust, cost-effective platform for synthetic cells. Using droplet microfluidics, we generate monodisperse Span 80-based GUNs that exhibit outstanding membrane fluidity and intrinsic selective permeability to small molecules (<400-500 Da) and protons, without the need for embedded transport proteins. We demonstrate their functional utility by inducing pH-responsive liquid-liquid phase separation to mimic membraneless organelles and by reconstituting a self-sustaining glycolysis-mitochondria cascade to fuel ATP-driven actin polymerization. These results establish GUNs as versatile, cost-effective, and permeable synthetic cell models, with broad potential in biomimetic microsystems, synthetic biology, and drug delivery.