N-Alcohol Length Governs Shift in L-L Mixing Temperatures in Synthetic and Cell-Derived Membranes

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2017 Aug 13

PMID 28801104

Citations 11

Authors

Caitlin E Cornell

Nicola L C McCarthy

Kandice R Levental

Ilya Levental

Nicholas J Brooks

Sarah L Keller

Affiliations

Soon will be listed here.

Abstract

A persistent challenge in membrane biophysics has been to quantitatively predict how membrane physical properties change upon addition of new amphiphiles (e.g., lipids, alcohols, peptides, or proteins) in order to assess whether the changes are large enough to plausibly result in biological ramifications. Because of their roles as general anesthetics, n-alcohols are perhaps the best-studied amphiphiles of this class. When n-alcohols are added to model and cell membranes, changes in membrane parameters tend to be modest. One striking exception is found in the large decrease in liquid-liquid miscibility transition temperatures (T) observed when short-chain n-alcohols are incorporated into giant plasma membrane vesicles (GPMVs). Coexisting liquid-ordered and liquid-disordered phases are observed at temperatures below T in GPMVs as well as in giant unilamellar vesicles (GUVs) composed of ternary mixtures of a lipid with a low melting temperature, a lipid with a high melting temperature, and cholesterol. Here, we find that when GUVs of canonical ternary mixtures are formed in aqueous solutions of short-chain n-alcohols (n ≤ 10), T increases relative to GUVs in water. This shift is in the opposite direction from that reported for cell-derived GPMVs. The increase in T is robust across GUVs of several types of lipids, ratios of lipids, types of short-chain n-alcohols, and concentrations of n-alcohols. However, as chain lengths of n-alcohols increase, nonmonotonic shifts in T are observed. Alcohols with chain lengths of 10-14 carbons decrease T in ternary GUVs of dioleoyl-PC/dipalmitoyl-PC/cholesterol, whereas 16 carbons increase T again. Gray et al. observed a similar influence of the length of n-alcohols on the direction of the shift in T. These results are consistent with a scenario in which the relative partitioning of n-alcohols between liquid-ordered and liquid-disordered phases evolves as the chain length of the n-alcohol increases.

Citing Articles

Coupling liquid phases in 3D condensates and 2D membranes: Successes, challenges, and tools.

Weakly H, Keller S Biophys J. 2023; 123(11):1329-1341.

PMID: 38160256 PMC: 11163299. DOI: 10.1016/j.bpj.2023.12.023.

Remodeling of yeast vacuole membrane lipidomes from the log (one phase) to stationary stage (two phases).

Reinhard J, Leveille C, Cornell C, Merz A, Klose C, Ernst R Biophys J. 2023; 122(6):1043-1057.

PMID: 36635960 PMC: 10111276. DOI: 10.1016/j.bpj.2023.01.009.

Heptanol-mediated phase separation determines phase preference of molecules in live cell membranes.

Gupta A, Lu D, Balasubramanian H, Chi Z, Wohland T J Lipid Res. 2022; 63(6):100220.

PMID: 35490741 PMC: 9160352. DOI: 10.1016/j.jlr.2022.100220.

High-Content Imaging Platform to Discover Chemical Modulators of Plasma Membrane Rafts.

Fricke N, Raghunathan K, Tiwari A, Stefanski K, Balakrishnan M, Waterson A ACS Cent Sci. 2022; 8(3):370-378.

PMID: 35355811 PMC: 8961798. DOI: 10.1021/acscentsci.1c01058.

Yeast cells actively tune their membranes to phase separate at temperatures that scale with growth temperatures.

Leveille C, Cornell C, Merz A, Keller S Proc Natl Acad Sci U S A. 2022; 119(4).

PMID: 35046036 PMC: 8795566. DOI: 10.1073/pnas.2116007119.

References

Rowe E, Zhang F, Leung T, Parr J, Guy P . Thermodynamics of membrane partitioning for a series of n-alcohols determined by titration calorimetry: role of hydrophobic effects. Biochemistry. 1998; 37(8):2430-40. DOI: 10.1021/bi9721602. View

Ionova I, Livshits V, Marsh D . Phase diagram of ternary cholesterol/palmitoylsphingomyelin/palmitoyloleoyl-phosphatidylcholine mixtures: spin-label EPR study of lipid-raft formation. Biophys J. 2012; 102(8):1856-65. PMC: 3328704. DOI: 10.1016/j.bpj.2012.03.043. View

Baumgart T, Hammond A, Sengupta P, Hess S, Holowka D, Baird B . Large-scale fluid/fluid phase separation of proteins and lipids in giant plasma membrane vesicles. Proc Natl Acad Sci U S A. 2007; 104(9):3165-70. PMC: 1805587. DOI: 10.1073/pnas.0611357104. View

Veatch S, Leung S, Hancock R, Thewalt J . Fluorescent probes alter miscibility phase boundaries in ternary vesicles. J Phys Chem B. 2007; 111(3):502-4. DOI: 10.1021/jp067636i. View

Barry J, Gawrisch K . Effects of ethanol on lipid bilayers containing cholesterol, gangliosides, and sphingomyelin. Biochemistry. 1995; 34(27):8852-60. DOI: 10.1021/bi00027a037. View

Blosser M, Starr J, Turtle C, Ashcraft J, Keller S . Minimal effect of lipid charge on membrane miscibility phase behavior in three ternary systems. Biophys J. 2013; 104(12):2629-38. PMC: 3686330. DOI: 10.1016/j.bpj.2013.04.055. View

Gray E, Diaz-Vazquez G, Veatch S . Growth Conditions and Cell Cycle Phase Modulate Phase Transition Temperatures in RBL-2H3 Derived Plasma Membrane Vesicles. PLoS One. 2015; 10(9):e0137741. PMC: 4569273. DOI: 10.1371/journal.pone.0137741. View

Magee A, Adler J, Parmryd I . Cold-induced coalescence of T-cell plasma membrane microdomains activates signalling pathways. J Cell Sci. 2005; 118(Pt 14):3141-51. DOI: 10.1242/jcs.02442. View

McCarthy N, Ces O, Law R, Seddon J, Brooks N . Separation of liquid domains in model membranes induced with high hydrostatic pressure. Chem Commun (Camb). 2015; 51(41):8675-8. DOI: 10.1039/c5cc02134k. View

10.

Chen S, Yang B, Jacobson K, Sulik K . The membrane disordering effect of ethanol on neural crest cells in vitro and the protective role of GM1 ganglioside. Alcohol. 1996; 13(6):589-95. DOI: 10.1016/s0741-8329(96)00073-0. View

11.

Huster D, Arnold K, Gawrisch K . Influence of docosahexaenoic acid and cholesterol on lateral lipid organization in phospholipid mixtures. Biochemistry. 1998; 37(49):17299-308. DOI: 10.1021/bi980078g. View

12.

Holowka D, Baird B . Structural studies on the membrane-bound immunoglobulin E-receptor complex. 1. Characterization of large plasma membrane vesicles from rat basophilic leukemia cells and insertion of amphipathic fluorescent probes. Biochemistry. 1983; 22(14):3466-74. DOI: 10.1021/bi00283a025. View

13.

Veatch S, Keller S . Separation of liquid phases in giant vesicles of ternary mixtures of phospholipids and cholesterol. Biophys J. 2003; 85(5):3074-83. PMC: 1303584. DOI: 10.1016/S0006-3495(03)74726-2. View

14.

Shen Y, Lindemeyer A, Gonzalez C, Shao X, Spigelman I, Olsen R . Dihydromyricetin as a novel anti-alcohol intoxication medication. J Neurosci. 2012; 32(1):390-401. PMC: 3292407. DOI: 10.1523/JNEUROSCI.4639-11.2012. View

15.

Janoff A, Pringle M, Miller K . Correlation of general anesthetic potency with solubility in membranes. Biochim Biophys Acta. 1981; 649(1):125-8. DOI: 10.1016/0005-2736(81)90017-1. View

16.

Baumgart T, Hunt G, Farkas E, Webb W, Feigenson G . Fluorescence probe partitioning between Lo/Ld phases in lipid membranes. Biochim Biophys Acta. 2007; 1768(9):2182-94. PMC: 2702987. DOI: 10.1016/j.bbamem.2007.05.012. View

17.

Levental K, Lorent J, Lin X, Skinkle A, Surma M, Stockenbojer E . Polyunsaturated Lipids Regulate Membrane Domain Stability by Tuning Membrane Order. Biophys J. 2016; 110(8):1800-1810. PMC: 4850323. DOI: 10.1016/j.bpj.2016.03.012. View

18.

Bagatolli L, Sanchez S, Hazlett T, Gratton E . Giant vesicles, Laurdan, and two-photon fluorescence microscopy: evidence of lipid lateral separation in bilayers. Methods Enzymol. 2003; 360:481-500. DOI: 10.1016/s0076-6879(03)60124-2. View

19.

Meerschaert R, Kelly C . Trace membrane additives affect lipid phases with distinct mechanisms: a modified Ising model. Eur Biophys J. 2015; 44(4):227-33. PMC: 4412547. DOI: 10.1007/s00249-015-1017-x. View

20.

Chin J, Goldstein D . Membrane-disordering action of ethanol: variation with membrane cholesterol content and depth of the spin label probe. Mol Pharmacol. 1981; 19(3):425-31. View