Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Apr 1;3(4):a004630.
doi: 10.1101/cshperspect.a004630.

Phase separation in lipid membranes

Frederick A Heberle  1 , Gerald W Feigenson
Affiliations
Review

Phase separation in lipid membranes

Frederick A Heberle et al. Cold Spring Harb Perspect Biol. .

Abstract

Cell membranes show complex behavior, in part because of the large number of different components that interact with each other in different ways. One aspect of this complex behavior is lateral organization of components on a range of spatial scales. We found that lipid-only mixtures can model the range of size scales, from approximately 2 nm up to microns. Furthermore, the size of compositional heterogeneities can be controlled entirely by lipid composition for mixtures such as 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/cholesterol or sphingomyelin (SM)/DOPC/POPC/cholesterol. In one region of special interest, because of its connection to cell membrane rafts, nanometer-scale domains of liquid-disordered phase and liquid-ordered phase coexist over a wide range of compositions.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Lattice snapshots for Monte Carlo simulations of binary mixtures with different pairwise interaction energy ΔEm. (A) A random mixture (ΔEm = 0) is characterized by groupings of 3 to 5 lipids. (B) An unfavorable interaction of ΔEm = 0.4 kT results in clusters of 10 to 20 lipids, or a domain size of ∼3 nm. (C) At ΔEm = 0.5 kT the system is close to phase separation. An enlargement of the snapshot (F) reveals large clusters composed of hundreds of lipids. (D) At ΔEm = 0.55 kT the clusters coalesce, indicating a phase transition. (E) ΔEm = 0.6 kT. The phase-separated mixture is characterized by a single domain of each phase.
Figure 2.
Figure 2.
Lattice snapshots for Monte Carlo simulations of ternary mixtures. (E) An equimolar binary α/β mixture with an unfavorable pairwise interaction energy ΔEαβ = 0.8kT is characterized by coexistence of α-rich and β-rich phases. (A–D) Although maintaining the ratio of components α and β, a third component, γ (which could be cholesterol), is added that interacts favorably with both α and β (ΔEαγ =−0.8 kT, ΔEβγ =−1.2 kT). (D) At χγ = 0.20, large clusters of β within the α-rich phase (and vice versa) are evident. (C) Long-range structure is broken up at χγ = 0.25. An enlargement of the snapshot (F) shows clusters of hundreds of lipids, and the uneven distribution of component γ (gray) between α-rich (white) and β-rich (black) clusters. Further addition of component γ reduces the size of clusters. (B) Snapshot for χγ = 0.30 and (A) χγ = 0.35.
Figure 3.
Figure 3.
Illustrative phase diagram for a ternary lipid mixture containing low- and high-melting temperature lipids and cholesterol. Tielines are shown in phase-coexistence regions, and the Ld + Lo critical point is marked with a star. The effect of cholesterol addition to Ld (arrow 1), Lβ (arrow 3), or phase-separated Ld + Lβ mixtures (arrow 2) is discussed in the text.
Figure 4.
Figure 4.
ESR reveals similarity of macroscopic and nanoscopic phase properties. Compositional trajectories run in the approximate direction of Ld + Lo tielines (see Fig. 3) and differ only in the identity of the low-TM lipid. Composition-dependent order parameters obtained from ESR spectral simulations in DSPC/DOPC/chol (triangles) and DSPC/POPC/chol (circles).
Figure 5.
Figure 5.
Confocal microscopy of giant unilamellar vesicles reveals interesting domain morphology in a four-component mixture that is intermediate in size between the smallest nanoscopic domains of DSPC/POPC/chol and the macroscopic domains of DSPC/DOPC/chol. Vesicle composition DSPC/DOPC/POPC/chol = 45/4.5/25.5/25. Scale bar 10 microns.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abney JR, Scalettar BA 1995. Fluctuations and membrane heterogeneity. Biophys Chem 57: 27–36 - PubMed
    1. Ali MR, Cheng KH, Huang J 2007. Assess the nature of cholesterol-lipid interactions through the chemical potential of cholesterol in phosphatidylcholine bilayers. Proc Natl Acad Sci 104: 5372–5377 - PMC - PubMed
    1. Ayuyan AG, Cohen FS 2006. Lipid peroxides promote large rafts: Effects of excitation of probes in fluorescence microscopy and electrochemical reactions during vesicle formation. Biophys J 91: 2172–2183 - PMC - PubMed
    1. Brewster R, Safran SA 2010. Line active hybrid lipids determine domain size in phase separation of saturated and unsaturated lipids. Biophys J 98: L21–L23 - PMC - PubMed
    1. Collins MD, Keller SL 2008. Tuning lipid mixtures to induce or suppress domain formation across leaflets of unsupported asymmetric bilayers. Proc Natl Acad Sci 105: 124–128 - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources

-