Biological and biomimetic membranes are based on lipid bilayers, which consist of two monolayers or leaflets. To avoid bilayer edges, which form when the hydrophobic core of such a bilayer is exposed to the surrounding aqueous solution, a single bilayer closes up into a unilamellar vesicle, thereby separating an interior from an exterior aqueous compartment. Synthetic nanovesicles with a size below 100 nanometers, traditionally called small unilamellar vesicles, have emerged as potent platforms for the delivery of drugs and vaccines. Cellular nanovesicles of a similar size are released from almost every type of living cell. The nanovesicle morphology has been studied by electron microscopy methods but these methods are limited to a single snapshot of each vesicle. Here, we review recent results of molecular dynamics simulations, by which one can monitor and elucidate the spatio-temporal remodeling of individual bilayers and nanovesicles. We emphasize the new concept of leaflet tensions, which control the bilayers\' stability and instability, the transition rates of lipid flip-flops between the two leaflets, the shape transformations of nanovesicles, the engulfment and endocytosis of condensate droplets and rigid nanoparticles, as well as nanovesicle adhesion and fusion. To actually compute the leaflet tensions, one has to determine the bilayer\'s midsurface, which represents the average position of the interface between the two leaflets. Two particularly useful methods to determine this midsurface are based on the density profile of the hydrophobic lipid chains and on the molecular volumes.

Condensate droplets are formed in aqueous solutions of macromolecules that undergo phase separation into two liquid phases. A well-studied example are solutions of the two polymers PEG and dextran which have been used for a long time in biochemical analysis and biotechnology. More recently, phase separation has also been observed in living cells where it leads to membrane-less or droplet-like organelles. In the latter case, the condensate droplets are enriched in certain types of proteins. Generic features of condensate droplets can be studied in simple binary mixtures, using molecular dynamics simulations. In this review, I address the interactions of condensate droplets with biomimetic and biological membranes. When a condensate droplet adheres to such a membrane, the membrane forms a contact line with the droplet and acquires a very high curvature close to this line. The contact angles along the contact line can be observed via light microscopy, lead to a classification of the possible adhesion morphologies, and determine the affinity contrast between the two coexisting liquid phases and the membrane. The remodeling processes generated by condensate droplets include wetting transitions, formation of membrane nanotubes as well as complete engulfment and endocytosis of the droplets by the membranes.

Giant lipid vesicles form unusual multispherical or \"multi-balloon\" shapes consisting of several spheres that are connected by membrane necks. Such multispherical shapes have been recently observed when the two sides of the membranes were exposed to different sugar solutions. This sugar asymmetry induced a spontaneous curvature, the sign of which could be reversed by swapping the interior with the exterior solution. Here, previous studies of multispherical shapes are reviewed and extended to develop a comprehensive theory for these shapes. Each multisphere consists of large and small spheres, characterized by two radii, the large-sphere radius, Rl, and the small-sphere radius, Rs. For positive spontaneous curvature, the multisphere can be built up from variable numbers Nl and Ns of large and small spheres. In addition, multispheres consisting of N*=Nl+Ns equally sized spheres are also possible and provide examples for constant-mean-curvature surfaces. For negative spontaneous curvature, all multispheres consist of one large sphere that encloses a variable number Ns of small spheres. These general features of multispheres arise from two basic properties of curvature elasticity: the local shape equation for spherical membrane segments and the stability conditions for closed membrane necks. In addition, the (Nl+Ns)-multispheres can form several (Nl+Ns)-patterns that differ in the way, in which the spheres are mutually connected. These patterns may involve multispherical junctions consisting of individual spheres that are connected to more than two neighboring spheres. The geometry of the multispheres is governed by two polynomial equations which imply that (Nl+Ns)-multispheres can only be formed within a certain restricted range of vesicle volumes. Each (Nl+Ns)-pattern can be characterized by a certain stability regime that depends both on the stability of the closed necks and on the multispherical geometry. Interesting and challenging topics for future studies include the response of multispheres to locally applied external forces, membrane fusion between spheres to create multispherical shapes of higher-genus topology, and the enlarged morphological complexity of multispheres arising from lipid phase separation and intramembrane domains.

Cellular membranes exhibit a fascinating variety of different morphologies, which are continuously remodeled by transformations of membrane shape and topology. This remodeling is essential for important biological processes (cell division, intracellular vesicle trafficking, endocytosis) and can be elucidated in a systematic and quantitative manner using synthetic membrane systems. Here, recent insights obtained from such synthetic systems are reviewed, integrating experimental observations and molecular dynamics simulations with the theory of membrane elasticity. The study starts from the polymorphism of biomembranes as observed for giant vesicles by optical microscopy and small nanovesicles in simulations. This polymorphism reflects the unusual elasticity of fluid membranes and includes the formation of membrane necks or fluid \'worm holes\'. The proliferation of membrane necks generates stable multi-spherical shapes, which can form tubules and tubular junctions. Membrane necks are also essential for the remodeling of membrane topology via membrane fission and fusion. Neck fission can be induced by fine-tuning of membrane curvature, which leads to the controlled division of giant vesicles, and by adhesion-induced membrane tension as observed for small nanovesicles. Challenges for future research include the interplay of curvature elasticity and membrane tension during membrane fusion and the localization of fission and fusion processes within intramembrane domains.