Lipid packing and cholesterol content regulate membrane wetting and remodeling by biomolecular condensates

Biomolecular condensates play a central role in cellular processes by interacting with membranes driving wetting transitions and inducing mutual remodeling. While condensates are known to locally alter membrane properties such as lipid packing and hydration, it remains unclear how membrane composition and phase state in turn affect condensate affinity. Here, we show that it is not only the membrane phase itself, but rather the degree of lipid packing that determines the condensate affinity for membranes. Increasing lipid chain length, saturation, or cholesterol content, enhances lipid packing, thereby decreasing condensate interaction. This regulatory mechanism is consistent across various condensate-membrane…