Abstract

The addition of trace molecules into membranes can significantly alter the morphology of the co-existing liquid phases and lipid phase transition temperature. Membrane additives may affect lipid phase dynamics through preferentially partitioning to the boundary between lipid phases or preferentially mixing into one lipid phase. The characteristic differences between these mechanisms are demonstrated here in a minimalistic nearest neighbor model to provide a framework for how slight changes to membrane composition may affect lipid-phase-dependent processes, such as lipid-raft formation, immunological signaling, and molecular sorting preceding endocytosis with coexisting liquid phases. Within the low mole fractions explored here (≤3 mol%), increasing the additive concentration linearly changed the phase miscibility temperature. Rotationally asymmetric Janus particles reduced the miscibility transition temperature for all fractions and degree of phase polarization. Rotationally symmetric additives, however, either increased or decreased the phase miscibility temperature depending on the phase preference of the additive. While most experimental molecules may contain aspects of both of these idealized additives, this model provides a broad framework to quantify the effects of membrane additives in regard to lipid phase preference, lipid-raft association, and contribution to lipid phase-dependent molecular sorting.Electronic supplementary materialThe online version of this article (doi:10.1007/s00249-015-1017-x) contains supplementary material, which is available to authorized users.

Highlights

  • The presence of coexisting liquid-ordered and liquid-disordered lipid phases has been implicated in diverse biological processes with high sensitivity to perturbations in membrane composition, tension, curvature, and temperature (Lingwood et al 2008)

  • Changes in phase miscibility with an increasing additive fraction are visibly obvious in images of the system configuration (Figs. 2, S5, S6)

  • The miscibility temperature is reduced for any phase polarization (p), while rotationally symmetric gray particles either increased or decreased Tmis depending on their gray value (g) (Figs. 3, S6)

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Summary

Introduction

The presence of coexisting liquid-ordered and liquid-disordered lipid phases has been implicated in diverse biological processes with high sensitivity to perturbations in membrane composition, tension, curvature, and temperature (Lingwood et al 2008). Trace membrane additives can disturb the lipid phase dynamics and the associated biological processes. Some additives possess rotational asymmetry, preferentially localize to the phase boundary, reduce the phase miscibility, decrease the miscibility transition temperature (Tmis), and act as linactants, 1D analogs of surfactants (Trabelsi et al 2008). Other membrane additives are rotationally symmetric, preferentially localize into one particular lipid phase, and may increase or decrease Tmis. The effects of membrane additives are quantified by the change to the lipid phase Tmis. The difference between a sample temperature and Tmis determines fundamental equilibrium qualities such as the correlation length of the coexisting phases (HonerkampSmith et al 2008; Palmieri and Safran 2013a) and the dynamics of the phase mobility (Honerkamp-Smith et al 2012; Palmieri and Safran 2013b)

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