Resilient Membranized Coacervates Formed through Spontaneous Wrapping of Heat‐Destabilized Lipid Bilayers around Coacervate Droplets

Abstract Membranes and the membraneless biocondensates help organize cells and work synergistically to drive cellular processes. Separately, membrane‐bound and membraneless compartments face difficulties as stable protocells or synthetic cell systems. Here, we present a new method to create membranized coacervates (MCs) for coacervates with any surface charge and a wide range of phospholipid membrane compositions. MCs are formed when liposomes, destabilized using heat and divalent ions, are mixed with coacervate dispersions. Unlike previous reports of hybrid coacervates surrounded by membranes, the MC membranes form an effective barrier also against small molecules, including calcein and TAMRA. The MC membranes provide excellent stability to the protocells at pH 2–10, salt concentrations of up to 0.5 м, hypotonic and hypertonic conditions, and repeated freeze‐thaw cycles. MCs performed better in all the tested conditions than both coacervates and liposomes. We attribute this behavior to the increased stability that coacervates and liposomes confer to each other when together. MC membranes are unilamellar and fluid, allowing lateral lipid diffusion, and the lipids are more densely packed compared to their corresponding liposomes. MCs can help us understand how stable primitive cells might have emerged and build advanced synthetic cells with enhanced stability and selectivity.