Cu²⁺-Mediated membrane property modulation and aggregation of membranized coacervates for facilitating diabetic wound...

Membranization of membraneless coacervates is emerging as a promising but challenging strategy for addressing their inherent limitations, including fusion, Ostwald ripening and environmental sensitivity. Engineering membranized coacervate protocells with triggerable membrane dynamics endows them with additional functionalities and dynamic regulatory capabilities in response to external or biological stimuli. Inspired by the regulatory role of metal ions on biomembrane properties in living cells, we developed a Cu²⁺-triggered strategy enabling dynamic and reversible membrane property modulation of membranized coacervates. The membranized coacervate was constructed through sequential deposition of a 1,2-dioleoyl-sn-glycero-3-phosphocholine phospholipid bilayer and catechol-functionalized phospholipids. The addition of Cu²⁺ ions then reduced membrane fluidity, enhanced selective biomolecular permeability of membranized coacervates, stabilized coacervate structures, and promoted the formation of ordered assemblies. This transition was reversed by the Cu²⁺ ions chelator ethylenediaminetetraacetic acid. Moreover, combined with the biomedical effects of Cu²⁺ ions, glucose oxidase-loaded assemblies exhibited pronounced potential for antimicrobial and diabetic wound therapy. Our study demonstrates a dynamic coacervate membrane design paradigm, aiming to provide the possibility of constructing advanced synthetic cell mimics and complex cell-like behaviors, and to expand the biomedical applications of coacervates.