Membrane-Mediated Interaction of Biomolecular Condensates at Biomembranes

Cellular organization is achieved through compartmentalization into membrane-bound organelles and biomolecular condensates, formed by liquid-liquid phase separation of biopolymers. These condensates behave as liquid droplets with interfacial tensions in the μN/m-mN/m range, and interact with lipid membranes by wetting and deforming them. Using the Helfrich Hamiltonian, triangulated interfaces and membranes, and energy minimization, we analyze the wetting-to-wrapping transition of single condensates at initially planar membranes. For a given membrane stiffness, when the ratio of condensate-cytosol interfacial tension to the membrane tension exceeds a critical value, with increasing adhesion strength, the condensates undergo multiple transitions between nonwrapped, shallow-wrapped, deep-wrapped, and complete-wetting states. The deep-wrapped state is characterized by a neck-stabilized morphology that suppresses complete wrapping; a transition to a complete-wetting state occurs at sufficiently high adhesion strength. At high ratios of the membrane tension over the condensate-cytosol interfacial tension, the deep-wrapped state vanishes at a triple point, and the condensates transition directly from shallow-wrapped to complete-wetting with increasing adhesion strength. Furthermore, we quantify membrane-mediated interactions between two partial-wrapped condensates. High membrane tension induces repulsion by reducing the adhered area at short separations, whereas low membrane tension promotes attraction via cooperative wrapping. Upon contact, the condensates fuse into a nearly spherical droplet, reflecting the dominance of interfacial tension over membrane bending. Overall, our results provide a quantitative framework for understanding condensate organization at biological membranes and guiding the design of biomolecular condensates for drug-delivery applications.