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

Cornell Affiliated Author(s)

Author

E.D. Mitra
S.C. Whitehead
D. Holowka
B. Baird
J.P. Sethna

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 kBT), whereas a membrane near a tricritical point can mediate a 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. © 2018 American Chemical Society.

Date Published

Journal

Journal of Physical Chemistry B

Volume

122

Issue

13

Number of Pages

3500-3513,

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045026231&doi=10.1021%2facs.jpcb.7b10695&partnerID=40&md5=5cf7a537df9e88239ce1e795b1a5eba6

DOI

10.1021/acs.jpcb.7b10695

Research Area

Group (Lab)

James Sethna Group

Funding Source

2T32GM008267
DMR-1312160
DMR-1719490
R01-AI018306
R01GM117552

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