Dynamic Duos: Coacervate‐Lipid Membrane Interactions in Regulating Membrane Transformation and Condensate Size

Abstract Biomolecular condensates interfacing with lipid membranes is crucial for several key cellular functions. However, the role of lipid membranes in regulating condensates in cells remains obscure. Here, in‐depth interactions between condensates and lipid membranes are probed and unraveled by employing cell‐mimetic systems like Giant unilamellar vesicles (GUVs). An unprecedented influence of the coacervate size and their electrostatic interaction with lipid membranes is revealed on the membrane properties and deformation. Importantly, these findings demonstrate that the large relative size of coacervates and minimal electrostatic interaction strength with membranes allow for budding transitions at the interface. Membranes act as nucleation site for coacervates when the charge‐charge interaction is high, giving a wrinkled vesicle surface appearance. Molecular diffusion property of lipids, quantified using Fluorescence recovery after photobleaching (FRAP), is modulated at the coacervate‐membrane interaction site restricting the coarsening of coacervates. Notably, these results reveal coacervate droplets are intertwined in between membrane folds and invaginations discerned using Transmission electron microscopy (TEM) and high‐resolution imaging, which further controls the dimension of droplets resembling size distributions observed in cells. Finally, these findings provide mechanistic insights of lipid bilayers controlling condensate sizes that play a prominent role in comprehending nucleation and localization of cellular condensates.