The proliferation of life on earth is based on the ability of single cells to divide into two daughter cells. During cell division, the plasma membrane undergoes a series of morphological transformations which ultimately lead to membrane fission. Here, we show that analogous remodeling processes can be induced by low densities of proteins bound to the membranes of cell-sized lipid vesicles. Using His-tagged fluorescent proteins, we are able to precisely control the spontaneous curvature of the vesicle membranes. By fine-tuning this curvature, we obtain dumbbell-shaped vesicles with closed membrane necks as well as neck fission and complete vesicle division. Our results demonstrate that the spontaneous curvature generates constriction forces around the membrane necks and that these forces can easily cover the force range found in vivo. Our approach involves only one species of membrane-bound proteins at low densities, thereby providing a simple and extendible module for bottom-up synthetic biology.

Giant unilamellar vesicles (GUVs) provide a direct connection between the nano-and the microregime. On the one hand, these vesicles represent biomimetic compartments with linear dimensions of many micrometers. On the other hand, the vesicle walls are provided by single molecular bilayers that have a thickness of a few nanometers and respond sensitively to molecular interactions with small solutes, biopolymers, and nanoparticles. These nanoscopic responses are amplified by the GUVs and can then be studied on much larger scales. Therefore, GUVs are increasingly used as a versatile research tool for basic membrane science, bioengineering, and synthetic biology. Conventional GUVs have one major drawback, however: they have only a limited capability to cope with external perturbations such as osmotic inflation, adhesion, or micropipette aspiration that tend to rupture the membranes. In contrast, cell membranes tolerate the same kinds of mechanical perturbations without rupture because the latter membranes are coupled to reservoirs of membrane area. Here, we introduce GUVs with membrane nanotubes as model systems that include such area reservoirs. To demonstrate the increased robustness of these tubulated vesicles, we use micropipette aspiration and changes in the osmotic conditions applied to phospholipid membranes doped with the glycolipid GM1. A quantitative comparison between theory and experiment reveals that the response of the GUVs is governed by the membranes' spontaneous tension, a curvature-elastic material parameter that describes the bilayer asymmetry on the nanoscale. Because of their increased robustness, GUVs with nanotubes represent improved research tools for membrane science, in general, with potential applications as storage and delivery systems and as cell-like microcompartments in bioengineering, pharmacology, and synthetic biology.

A lipid vesicle exposed to an interior sucrose and an exterior glucose solution can attain a variety of multispherical shapes with different numbers of large and small spheres. For each shape, all spheres are connected by narrow membrane necks.

Biological cells are contained by a fluid lipid bilayer (plasma membrane, PM) that allows for large deformations, often exceeding 50% of the apparent initial PM area. Isolated lipids self‐organize into membranes, but are prone to rupture at small (<2–4%) area strains, which limits progress for synthetic reconstitution of cellular features. Here, it is shown that by preserving PM structure and composition during isolation from cells, vesicles with cell‐like elasticity can be obtained. It is found that these plasma membrane vesicles store significant area in the form of nanotubes in their lumen. These act as lipid reservoirs and are recruited by mechanical tension applied to the outer vesicle membrane. Both in experiment and theory, it is shown that a “superelastic” response emerges from the interplay of lipid domains and membrane curvature. This finding allows for bottom‐up engineering of synthetic biomaterials that appear one magnitude softer and with threefold larger deformability than conventional lipid vesicles. These results open a path toward designing superelastic synthetic cells possessing the inherent mechanics of biological cells.