Bending-mediated superstructural organizations in phase-separated lipid membranes

Lipid bilayers consisting of natural lipids and cholesterols can phase-separate into two immiscible fluid phases. These phases can further get organized into elaborated patterned superstructures, hexagonal arrays and stripes, of about micron periodicity. These periodic patterns must be maintained by a macroscopic inter-domain repulsion that competes with interfacial tension and they are not predicted for systems with pair-wise molecular interactions. Herein, we present simultaneous topography and fluorescence imaging of two-phase membranes that reveal the role of membrane bending mechanics in superstructural organizations. We observe that two-phase membranes are all curved. Real-time imaging demonstrates that these curved domains repel each other by bending the intervening region to the opposite direction. This type of macroscopic mechanical interaction may contribute to spatial organization in live cell membranes that cannot be explained solely by microscopic intermolecular interactions and phase separations, such as spatial organization of signaling molecules and their coupling to topography observed in endocytotic pits or intercellular junctions.