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
. 2007 Nov 6;104(45):17650-5.
doi: 10.1073/pnas.0703513104. Epub 2007 Oct 25.

Critical fluctuations in domain-forming lipid mixtures

Sarah L Veatch  1 , Olivier Soubias, Sarah L Keller, Klaus Gawrisch
Affiliations

Critical fluctuations in domain-forming lipid mixtures

Sarah L Veatch et al. Proc Natl Acad Sci U S A. .

Abstract

Critical fluctuations are investigated in lipid membranes near miscibility critical points in bilayers composed of dioleoylphosphatidylcholine, chain perdeuterated dipalmitoylphosphatidylcholine, and cholesterol. Phase boundaries are mapped over the temperature range from 10 degrees C to 60 degrees C by deuterium NMR. Tie-lines and three-phase triangles are evaluated across two-phase and three-phase regions, respectively. In addition, a line of miscibility critical points is identified. NMR resonances are broadened in the vicinity of critical points, and broadening is attributed to increased transverse relaxation rates arising from modulation of chain order with correlation times on a microsecond time scale. We conclude that spectral broadening arises from composition fluctuations in the membrane plane with dimensions of <50 nm and speculate that similar fluctuations are commonly found in cholesterol-containing membranes.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
2H NMR spectra of DPPC-d62 in membranes of DOPC/DPPC-d62/Chol. (a–f) 2H NMR spectra of DPPC-d62 in multilamellar vesicles of various DOPC/DPPC-d62/Chol compositions acquired at 20°C with phase assignments as described in the text. Membrane compositions are in the form DOPC:DPPC-d62 plus % Chol: a, 4:1 plus 15%; b, 4:1 plus 40%; c, 2:1 plus 25%; d, 1:1 plus 15%; e, 1:2 plus 25%; f, 1:4 plus 10%. (g–l) Spectra for membranes of 1:2 DOPC/DPPC-d62 plus 20% Chol at the temperatures indicated.
Fig. 2.
Fig. 2.
Tie-lines, three-phase triangles, and spectral broadening in membranes of DOPC/DPPC-d62/Chol. (a–d) Tie-lines across two-phase regions and endpoints of the three-phase triangles are determined for multilamellar vesicles of DOPC/DPPC-d62/Chol. Errors on tie-lines and three-phase triangles are shown. Transition temperatures and calculated endpoints are shown in SI Tables 1–3. (e–h) Phase data are superimposed on a colored surface indicating a spectral width of 2H NMR methyl resonances as a function of lipid composition, demonstrating that broadening occurs near known miscibility critical points. Small symbols indicate the phase state of acquired spectra.
Fig. 3.
Fig. 3.
Phase diagrams of DOPC/DPPC-d62/Chol. (a) A constant temperature cut through the ternary phase diagram at 10°C shows phase assignments. The liquid–liquid (Ld-Lo) coexistence region is shaded blue and terminates in a critical point at the yellow circle. At low cholesterol, the Ld-Lo region is bounded by a three-phase triangle shaded green, in which Ld, Lo, and So phases coexist. The three-phase triangle is connected to two separate regions of solid–liquid coexistence (Lo-So and Ld-So), which are shaded red. (b) Multiple constant-temperature phase diagrams are assembled into a three-dimensional ternary phase diagram spanning 10°C and 37°C, with the dashed yellow line approximating a line of critical points.
Fig. 4.
Fig. 4.
Increased transverse relaxation rates (R2) but not longitudinal relaxation rates (R1) are found in membranes of 1:2 DOPC/DPPC-d62 plus 20% Chol in the vicinity of the miscibility critical point (≈30°C). (a and b) Relaxation rates are measured from 2H nuclei. (c and d) Similar trends in relaxation rates occur in the methylene groups of DOPC measured by 1H MAS NMR. (e) 2H MAS NMR relaxation measurements also indicate that line-broadening is dominated by increased R2 values. ( f) Critical features of the acquired static 2H NMR spectrum at 30°C (gray) are reproduced by a simulated spectrum (black) that assumes spectral broadening is dominated by values of R2 from a, as is described in Materials and Methods.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Dietrich C, Bagatolli LA, Volovyk ZN, Thompson NL, Levi M, Jacobson K, Gratton E. Biophys J. 2001;80:1417–1428. - PMC - PubMed
    1. Samsonov AV, Mihalyov I, Cohen FS. Biophys J. 2001;81:1486–1500. - PMC - PubMed
    1. Chapman D, Penkett SA. Nature. 1966;211:1304–1305. - PubMed
    1. Darke A, Finer EG, Flook AG, Phillips MC. J Mol Biol. 1972;63:265–279. - PubMed
    1. Oldfield E, Chapman D. FEBS Lett. 1972;23:285–297. - PubMed

Publication types