Receptor-mediated signaling through a prewetting phase-transition*

Membrane-bound receptors sense ligands at the plasma membrane, and must amplify and communicate the signals they receive into the three-dimensional cytoplasm. Proteins involved in these signaling cascades often form "signaling clusters" upon activation: structures rich in many of the 3D components required for downstream signaling, as well as specific lipids and membrane bound proteins. Recent work has suggested that liquid-liquid phase separation underpins many signaling clusters. Here we develop a theory of these phenomena through Monte-Carlo simulations and a minimal Landau theory. Our model suggests that signaling clusters are best described as prewet, displaying surface-only phase coexistence outside of the ordinary membrane and bulk protein coexistence regions[1]. Prewet phases confer the ability to 'integrate' the state of the bulk and membrane concurrently. We explore the ramifications of our model wherein signal initially received at many receptors is integrated and transduced by the dynamics of the prewetting transition.