Cells can precisely
program the shape and lateral organization
of their membranes using protein machinery. Aiming to replicate a
comparable degree of control, here we introduce DNA-origami line-actants
(DOLAs) as synthetic analogues of membrane-sculpting proteins. DOLAs
are designed to selectively accumulate at the line-interface between
coexisting domains in phase-separated lipid membranes, modulating
the tendency of the domains to coalesce. With experiments and coarse-grained
simulations, we demonstrate that DOLAs can reversibly stabilize two-dimensional
analogues of Pickering emulsions on synthetic giant liposomes, enabling
dynamic programming of membrane lateral organization. The control
afforded over membrane structure by DOLAs extends to three-dimensional
morphology, as exemplified by a proof-of-concept synthetic pathway
leading to vesicle fission. With DOLAs we lay the foundations for
mimicking, in synthetic systems, some of the critical membrane-hosted
functionalities of biological cells, including signaling, trafficking,
sensing, and division.