Spontaneous wrapping of coacervates by lipid bilayers upon heat shock creates resilient and intact membranized coacervates

Membranes and 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 3-11, salt concentrations up to 0.5 M, hypotonic and hypertonic conditions, and repeated freeze-thaw cycles. MCs performed better in all the tested conditions than both coacervates and liposomes. We ascribe this behavior to the increased stability that coacervates and liposomes confer to each other when together. MC membranes are fluid, allowing lateral lipid diffusion, but the lipids are more densely packed compared to their corresponding liposomes. MCs can help us understand how stable primitive cells might have formed, and help us build advanced synthetic cells with enhanced stability and selectivity.