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Lipid phase heterogeneity in the plasma membrane is thought to be crucial formany aspects of cell signaling, but the physical basis of participatingmembrane domains such as "lipid rafts" remains controversial. Here we considera lattice model yielding a phase diagram that includes several states proposedto be relevant for the cell membrane, including microemulsion - which can berelated to membrane curvature - and Ising critical behavior. Using a neuralnetwork-based machine learning approach, we compute the full phase diagram ofthis lattice model. We analyze selected regions of this phase diagram in thecontext of a signaling initiation event in mast cells: recruitment of themembrane-anchored tyrosine kinase Lyn to a cluster of transmembrane ofIgE-Fc{\epsilon}RI receptors. We find that model membrane systems inmicroemulsion and Ising critical states can mediate roughly equal levels ofkinase recruitment (binding energy ~ -0.6 kBT), whereas a membrane near atricritical point can mediate much stronger kinase recruitment (-1.7 kBT). Bycomparing several models for lipid heterogeneity within a single theoreticalframework, this work points to testable differences between existing models. Wealso suggest the tricritical point as a new possibility for the basis ofmembrane domains that facilitate preferential partitioning of signalingcomponents.

Computation of a Theoretical Membrane Phase Diagram, and the Role of Phase in Lipid Raft-Mediated Protein Organization