Wetting of Critical Membranes by Protein Droplets

Phase-separated liquid-droplets of protein and RNA have recently been found as ubiquitous structures in cells – coordinating reactions, organizing cellular machinery, and protecting sensitive biomolecules. In two dimensions, the plasma membrane is organized by heterogeneities in lipid composition, with membrane domains posited to be a consequence of proximity to a miscibility critical point. These structures are linked by components that interact with both 2D and 3D phases such as lipidated proteins that partition into specific membrane phases. This leads protein droplets to localize to particular membrane domains, as seen in the post-synaptic structure, the immunologic synapse, and components of cell adhesion. Here, we consider the underlying thermodynamics of this interaction, constructing a minimal Landau theory describing the wetting of protein droplets to a near-critical membrane. The resulting phase diagram shows non-standard wetting behavior, where surface criticality greatly enhances a prewetting-like regime where bulk and surface phase separate together. We buttress these theoretical predictions with simulations of nearly critical Ising surfaces coupled to coacervating lattice polymers and link existing experimental observations to this phase diagram.