Selective membrane wetting of phase-separated giant unilamellar vesicles by coacervate droplets

Liquid-liquid phase separation (LLPS) has emerged as a key biological paradigm, playing a critical role in cellular compartmentalization and potentially contributing to the origins of life. Lipid membranes are equally important in these processes, serving as selective barriers that define and protect cellular environments. Recent studies have revealed a dynamic interaction between LLPS and lipid membranes, both in cellulo and in biomimetic systems. In vitro studies typically use simplified model membranes, while biological membranes are far more complex, often exhibiting phase-separated domains. Despite growing interest, the relationship between lipid phase separation within membranes and LLPS remains largely unexplored. Here, we explore how coacervates interact with membranes composed of liquid-ordered or liquid-disordered lipid phases using giant unilamellar vesicles (GUVs). We show that coacervate-membrane interactions are modulated by coacervate composition and lipid domain properties. Notably, we report the selective wetting of lipid domains in phase separated GUVs. Different coacervates exhibit distinct wetting behaviors, with variations in their composition influencing whether they preferentially wet liquid-disordered or liquid-ordered lipid domains, highlighting the coacervate-specific nature of these interactions. These findings highlight how lipid phase separation can mediate selective membrane wetting, offering insights into condensate-membrane interactions in cells and in simplified cell-like model systems.