Biomolecular condensates in contact with membranes: interaction mechanism, wetting, and complex remodeling

Membrane wetting by biomolecular condensates recently emerged as an important phenomenon in cell biology. It plays a vital role in a diverse range of processes across different organisms. However, the potential of membrane remodeling and the underlying mechanisms are not well understood. Here, we performed a systematic analysis of the interaction of protein and polymer condensates with giant unilamellar vesicles as model membranes. We demonstrate that these interactions can lead to striking morphological transformations, which are elucidated by theoretical analysis. A remarkable phenomenon, namely fingering or ruffling of the condensate-membrane interface is observed when sufficient membrane area is available. We resolve these intricately curved structures with STED. The observed morphologies are governed by the interplay of adhesion, membrane elasticity, and interfacial tension. Using nano-environmental sensors and state-of-the-art microscopy techniques combined with phasor analysis, we find that biomolecular condensates can modulate membrane lipid packing and hydration by wetting. This discovery has important implications for understanding how cells regulate their membrane properties and could pave the way for new approaches to the manipulation of cellular processes.