Cell membranes are central to life, yet most synthetic membrane mimics remain constrained by the logic of lipids: structure and function are largely decoupled, with functionality added through separate components such as proteins or functional lipids. In this work, we introduce pepticombisomes, a fundamentally new concept for synthetic cell membranes in which the structural backbone itself becomes an information-rich and functional element. Pepticombisomes are vesicles assembled from recombinant supercharged unfolded polypeptides complexed with lipid-like surfactants. Unlike liposomes or polymersomes, their membranes are built from sequence-defined peptide backbones, ensuring molecular uniformity in composition, topology, and spontaneous curvature. This precision enables the formation of giant unilamellar vesicles with biomimetic thickness and exceptional flexibility, matching or surpassing lipid membranes while retaining high stability.
Crucially, functionality is no longer confined to add-on components: the peptide backbone encodes mechanical properties, lateral interactions, and elastic heterogeneities through its sequence and hydrogen-bonding capability. As a result, membrane behavior—such as extreme flexibility or localized faceting— emerges directly from backbone design, without requiring gel phases or complex multicomponent mixtures.
By shifting membrane design from lipid chemistry to programmable polypeptide backbones, this work demonstrates how membrane structure, mechanics, and potential functionality can be co-encoded within a single molecular architecture. This perspective opens new directions for synthetic biology, where membranes are no longer passive barriers but designed, information-bearing scaffolds for future synthetic cells and biointerfaces.
