Complex remodeling of biomembranes and vesicles by condensate droplets†

Condensate droplets are formed by liquid–liquid phase separation in aqueous solutions of macromolecules such as polymers and proteins. Here, we look at the interactions of such droplets with biomembranes, integrating the results of recent experimental studies and computer simulations into the theoretical framework of fluid elasticity. The droplets can be formed via segregative or associative phase separation. It is argued that the corresponding phase diagrams exhibit one or two critical demixing points at constant temperature and that the vicinity of such a critical point leads to complete wetting of the membranes by the droplets. In general, both exterior and interior droplets can exhibit different wetting geometries, characterized by three apparent contact angles on the scale of a few hundred nanometers, as resolved by conventional light microscopy, and by two intrinsic contact angles on the scale of a few tens of nanometers. In response to a reduction of vesicle volume or to an increase of membrane area, the vesicle–droplet systems undergo a variety of remodeling processes, such as complete engulfment of the droplets or nanotubulation of the membranes. The closure of membrane necks adjacent to condensate droplets can proceed via several distinct morphological pathways. For partial wetting, the nanotubes adhere to the liquid–liquid interfaces and can then transform into double-membrane sheets.