Equilibrium microphase separation in the two-leaflet model of lipid membranes

Abstract

Because of the coupling between local lipid composition and the thickness of the membrane, microphase separation in two-component lipid membranes can take place; such effects may underlie the formation of equilibrium nanoscale rafts. Using a kinetic description, this phenomenon is analytically and numerically investigated. The phase diagram is constructed through the stability analysis for linearized kinetic equations, and conditions for microphase separation are discussed. Simulations of the full kinetic model reveal the development of equilibrium membrane nanostructures with various morphologies from the initial uniform state. DOI: 10.1103/PhysRevE.93.010401 The idea of membrane nanodomains forming lipid rafts [1], although controversial, has been useful as a basic organizing principle to understand the connection between membrane structure and functionality [2]. Despite broad experimental evidence supporting nanoscale raft organization, clear understanding of its physical origin still remains under debate [3]. Generally, there are two scenarios that may account for prevention of complete phase separation in binary solutions and development of stationary finite-size domains. At equilibrium, such domains can arise from the microphase separation resulting from the competition between attractive local and repulsive long-ranged interactions between particles [4]. In nonequilibrium systems, an analog of the microphase separation can be observed when energetically activated reactions between two components are included [5,6]. The nonequilibrium scenario has inspired a variety of proposals in the context of the cell membrane [7][8][9][10][11][12].Equilibrium microphase separation in two-component lipid membranes was found in two-leaflet models with different lipid composition in each leaflet [13][14][15][16]. In these models, coupling between the local membrane curvature and the difference of local lipid compositions in two layers could give rise to an instability at finite wave numbers. In the resulting modulated phases, lipid variations were, however, anticorrelated between the two layers, in contrast to the correlation or domain registration, expected for lipid rafts. Recent computer simulations of molecular coarse-grained models for two-component lipid bilayers have also shown that correlated (registered) nanodomains with similar local composition in both leaflets can be observed [17]. To explain this, a mechanism that additionally allows for local changes of the membrane thickness has been proposed [17,18] and the minimization of the free energy using the Brazovskii approximation has shown that modulated phases with identical lipid composition in the leaflets are possible in this case [18].In this Rapid Communication, the kinetic two-leaflet model for the mechanism [17,18] is constructed and investigated. By direct stability analysis, general conditions for microphase * reigada@ub.edu separation are obtained and the phase transition diagram is determined. Nonlinear simulations of various emerging nanostructur...

Direct observations of transition dynamics from macro- to micro-phase separation in asymmetric lipid bilayers induced by externally added glycolipids

“…-In general, phase separation in binary liquid mixtures completes by relaxation below the transition temperature. However, it is also well known that the competition between local attractive and long-ranged repulsive interactions between two phases leads to stable micro-phase separation [1][2][3][4][5][6][7]. The coarsening dynamics from a homogeneous phase to macro-or micro-phase has been extensively investigated in binary mixture systems of polymeric and/or low-molecular-weight molecules [3,4,8].…”

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“…Reigada and Mikhailov [164] have recently carried out a linear stability analysis and dynamic Ginzburg-Landau simulations of a monolayer curvature coupling model and calculated a phase diagram in a different plane of parameters than Fig. 8.…”

Hydrodynamic collective effects of active proteins in biological membranes

“…It has been suggested that equilibrium nanoscale rafts can result from micro-phase separation effects that are observed when interactions between the two layers in a membrane are taken into account (see, e.g., Refs. [11][12][13][14]).…”