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

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 IgE-FcεRI 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 k T), whereas a membrane near a tricritical point can mediate a much stronger kinase recruitment (-1.7 k T). 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.

Lipid-based, protein-based, and steric interactions synergize to facilitate transmembrane signaling stimulated by antigen-clustering of IgE receptors

“…The role of lipids in stimulated Lyn/IgE-FcεRI coupling has been scrutinized in experimental (15,(17)(18)(19) and theoretical (20) studies over two decades, yielding the view that Ag-crosslinking stabilizes liquid ordered (Lo)-like nanodomains around the clustered IgE-FcεRI. Referred to commonly (and roughly) as "rafts," these proteo-lipid organizational features of plasma membranes have variable properties that depend on cellular circumstance but generally resemble Lo domains that co-exist with liquid disordered (Ld) regions at equilibrium in model membranes of defined composition (21).…”

Lattice Models for Protein Organization throughout Thylakoid Membrane Stacks

“…The spirit of our approach echoes many previous efforts to understand basic physical mechanisms of collective behavior in membrane systems, from lipid domain formation to correlations among sites pinned by proteins or substrates (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(45)(46)(47)(48)(49)(50)(51). By stripping away most molecular details, simplified descriptions of phase transitions such as spin models and field theories focus attention on the emergence of dramatic macroscopic response from a few microscopic ingredients.…”

“…The computational works mentioned above utilize coarsegrained particle approaches, whereas our model will be a lattice-based approach; in this manner, we attempt to create the simplest possible explanatory model for vertical ordering in photosynthetic membranes (9,(16)(17)(18). Lattice models have been used for myriad studies of lipid organization in bilayers, as well as for lipid-protein membrane systems (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37).…”

Intelligent fluorescence image analysis of giant unilamellar vesicles using convolutional neural network

“…It has been proven to be powerful in descriptor extraction and classification for visual recognition tasks [ 19 ]. Because of recent progress in deep learning, its capability and efficiency reach even beyond human recognition, and it has been applied to a wide range of related fields in leading-edge science and engineering [ 20 – 28 ]. Classifying the objects is a very common task needed in image analysis.…”