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Article citations


Wang, W., Yang, L. and Huang, H.W. (2007) Evidence of cholesterol accumulated in high curvature regions: implication to the curvature elastic energy for lipid mixtures. Biophysical Journal, 92, 2819-2830. doi:10.1529/biophysj.106.097923

has been cited by the following article:

  • TITLE: Coarse-grained simulations of branched bilayer membranes: effects of cholesterol-dependent phase separation on curvature-driven lipid sorting

    AUTHORS: Manami Nishizawa, Kazuhisa Nishizawa

    KEYWORDS: Lipid Raft; Stalk Formation; Membrane Rigidity; Lipid Clustering; Lipid Sorting; Lipid Mixing; Hemifusion; Cholesterol-Rich Microdomain

    JOURNAL NAME: Journal of Biophysical Chemistry, Vol.2 No.3, August 11, 2011

    ABSTRACT: Our recent coarse-grained (CG) molecular dynamics (MD) simulations of membranes with a hemifused-ribbon (λ-shaped) geometry showed curvature-driven demixing leading to enrich ment in dioleoyl-phosphatidylethanolamine (DOPE) in a negatively-curved region (at C = –0.8 nm–1) of a DOPE/dipalmitoyl-phosphati-dylcholine (DPPC) membrane. Here we extend the analysis with respect to lipid composition and simulation time. Simulations of 12 – 20 μs effective time show that, compared with DOPE of the DOPE/DPPC system, a DPPC/dilinoleyl-PC [di(18:2)PC] membrane showed a similar degree of enrichment of di(18:2)PC in the curved region with C=–0.8 nm–1. For the latter mixture, even weak negative curvatures (C=–0.5 – 0.6 nm–1) caused significant degrees of di(18:2)PC enrichment. In agreement with recent studies of a planar bilayer, a ternary DPPC/ di(18:2)PC/cholesterol 0.42:0.28:0.3 mixture phase-separated into nanoscale raft-like liquid-ordered (Lo) and non-raft liquid-disordered (Ld) phases on a sub-microsecond time scale. The Lo domains were preferentially localized at planar portions, whereas the Ld domains were positioned mainly in curved regions of the membrane. Unlike binary dioleoylphosphatidylcho-line (DOPC)/cholesterol and DPPC/cholesterol mixtures, which showed only a slight enrich ment of cholesterol in the curved region, the ternary mixtures showed considerable migra tion of cholesterol and DPPC from the curved to the planar region. A pronounced degree of lipid segregation due to the preferential distribution of the Ld and Lo domains in the curved and planar regions, respectively, was observed even when the curvature of the fused monolayers (originally ‘cis’ leaflets) was weakened (C= –0.5 nm-1). Overall, the results are consistent with theoretical predictions based on spontaneous curvature of the constituent lipids and the difference in rigidity between the Ld and Lo domains, whereas lipid-lipid interactions, such as PE-PE or DPPC-cholesterol, as well as propensity for interleaflet colocalization (registration) of the Lo and Ld domains appear to significantly amplify curvature-induced lipid demixing in the λ system. Intriguingly, for the DPPC/ di(18:2)PC/cholesterol ternary mixtures, a Lo/Ld domain boundary often moved to the branched point of the membrane, suggesting enhanced flexibility at the domain boundary. We hypothesize that curvature-driven lipid sorting and energetically favored localization of domain boundaries at sharp bends in the membranes may collaborate to assist intracellular lipid sorting.