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

TL;DR

This study uses a lattice model and machine learning to explore membrane phase diagrams, revealing how different membrane states influence protein recruitment and proposing the tricritical point as a key factor in membrane domain formation.

Contribution

It introduces a neural network-based method to compute the phase diagram of a membrane model, linking phase states to protein recruitment in cell signaling.

Findings

Microemulsion and Ising critical states mediate similar kinase recruitment.

A membrane near a tricritical point enhances kinase recruitment significantly.

The work compares different models of lipid heterogeneity within a unified framework.

Abstract

Lipid phase heterogeneity in the plasma membrane is thought to be crucial for many aspects of cell signaling, but the physical basis of participating membrane domains such as "lipid rafts" remains controversial. Here we consider a lattice model yielding a phase diagram that includes several states proposed to be relevant for the cell membrane, including microemulsion - which can be related to membrane curvature - and Ising critical behavior. Using a neural network-based machine learning approach, we compute the full phase diagram of this lattice model. We analyze selected regions of this phase diagram in the context of a signaling initiation event in mast cells: recruitment of the membrane-anchored tyrosine kinase Lyn to a cluster of transmembrane of IgE-Fc{\epsilon}RI receptors. We find that model membrane systems in microemulsion and Ising critical states can mediate roughly equal levels of kinase recruitment (binding energy ~ -0.6 kBT), whereas a membrane near a tricritical point can mediate much stronger kinase recruitment (-1.7 kBT). By comparing several models for lipid heterogeneity within a single theoretical framework, this work points to testable differences between existing models. We also suggest the tricritical point as a new possibility for the basis of membrane domains that facilitate preferential partitioning of signaling components.