Konyakhina, TM and Feigenson GW. 2016. Phase Diagram of a Polyunsaturated Lipid Mixture: brain sphingomyelin/1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine/cholesterol. Biochim.Biophys.Acta. 1858: 153-161. PMID:4664456
For the first time, the phase diagram has been determined of a 3-component mixture containing a polyunsaturated phospholipid. Given the many reports of poor interactions of polyunsaturated acyl chains with cholesterol and other lipids, it might be surprising that this phase diagram is very similar to those of other 3-component lipid mixtures of the type: hi-Tm/low-Tm/chol.
Ackerman DG and Feigenson GW. 2015. Multiscale modeling of four-component lipid mixtures: Domain composition, size, alignment, and properties of the phase interface. J.Phys.Chem.B 119: 4240-4250. PMID:25564922
Domain size and domain alignment in the two leaflets change sharply over a narrow range of composition. At the Ld/Lo interface, lipids in each phase are only perturbed within about 2nm of the interface.
Amazon JJ and Feigenson GW. 2014. Lattice simulations of phase
morphology on lipid bilayers: Renormalization, membrane shape, and electrostatic dipole interactions.
When lipid bilayer Lo + Ld domains are as small as tens of nanometers, this small size can be explained by competition between Lo/Ld line tension vs bending energies and dipole-dipole repulsions. Coarse-grained simulations that span a large range of size scales must properly renormalize the line tension. Patterned domains in a curved bilayer form when the difference in bending energies between Lo and Ld domains is sufficiently large.
Heberle FA, Doktorova M, Goh SL, Standaert
RF, Katsaras J, and Feigenson GW. 2013. Hybrid and nonhybrid lipids exert common effects on membrane raft size and morphology.
J. Am. Chem. Soc., DOI: 10.1021/ja407624c
Mixtures of DSPC/DLPC/DOPC/chol, consisting of entirely nonhybrid lipids, behave almost identically to mixtures with common hybrid lipids such as POPC. We conclude that emphasis on a special behavior of hybrid lipids in forming nanodomains is misleading.
Konyakhina TM, Wu J, Mastroianni JD, Heberle FA, and Feigenson
GW. 2013. Phase Diagram of a 4-Component Lipid Mixture:
DSPC/DOPC/POPC/chol. Biochim. Biophys. Acta.,
A lipid-only mixture can transition between nano and macro phase
domains depending on acyl chain type of the low-melting lipids. The 4-component phase diagram shows that Ld + Lo nanodomains occur within a narrow, well-defined volume of the same phase region where macrodomains are found.
Ackerman D, Heberle FA, and Feigenson GW. 2013. Limited
perturbation of a DPPC bilayer by fluorescent lipid probes: A
molecular dynamics study. J. Phys. Chem. B., 117: 4844-4852. PMID:23548205
An often used indocarbocyanine fluorescent probe, DiI, is found to influence the order of its local 6-lipid environment by about 10% , but has very little effect on more distant lipids.
Heberle FA, Petruzielo RS, Pan J, Drazba P, Kucerka N, Standaert
RF, Feigenson GW, and Katsaras J. 2013. Bilayer thickness
mismatch controls domain size in model membranes.
J. Am. Chem. Soc., 135: 6853-6859. PMID: 23391155
This small-angle neutron scattering study of coexisting Ld + Lo phases shows nanodomain size around 15 nanometers, which increases as the line tension increases.
Petruzielo RS, Heberle FA, Drazba P, Katsaras J, and Feigenson GW. 2013. Phase Behavior and Domain Size in Sphingomyelin-Containing Lipid Bilayers. Biochim. Biophys. Acta., 1828: 1302-1313. PMID: 23337475
The phase diagrams of SM/DOPC/chol and SM/POPC/chol are found to be surprisngly similar for all phase boundaries. With SM from brain, nanodomain size of 7 nm is much smaller than nanodomain size of about 15 nm measured with SM from egg, or SM with palmitoyl or stearoyl chains.
Goh SL, Amazon J, and Feigenson GW. 2013. Towards a better raft
model: Modulated phases in the 4-component bilayer,
DSPC/DOPC/POPC/CHOL. Biophys. J., 104:853-862. PMID: 23442964
A large region of composition space exhibits patterned phase coexistence of Ld + Lo domains. In this region domain areas follow the Phase Rule, and are well-simulated by a model of competing interaction.
Amazon JJ, Goh SL, and Feigenson GW. 2013. Competition between line tension and curvature stabilizes modulated phase patterns on the surface of giant unilamellar vesicles. A simulation study. Phys. Rev. E., 87: 022708
A new method to simulate the observed patterns of Ld + Lo phase coexistence is described for the case of bending energies competing with line tension on GUVs.
Dick RA, Goh SL, Feigenson GW, and Vogt VM. 2012. HIV-1 Gag Protein Can Sense the Cholesterol and Acyl Chain Environment in Model Membranes. Proc. Natl. Acad. Sci. U S A., 109:18761-6. PMID: 23010924
The Gag protein, which forms the lattice that is the initial virion structure, is surprisingly sensitve to details of lipid bilayer acyl chains and cholesterol fraction.
Dai J, Alwarawrah M, Ali MR, Feigenson GW and Huang J. 2011. Simulation of the lo-ld phase boundary in DSPC/DOPC/cholesterol ternary mixtures using pairwise interactions. J. Phys. Chem. B., 115:1662-1671. PMID: 21271714
Monte Carlo simulations using only pairwise additive interactions are reasonably good at reproducing experimental phase boundaries, but clearly show that multibody interactions occur.
Konyakhina TM, Goh SL, Amazon J, Heberle FA, Wu J and Feigenson GW. 2011. Control of a
nanoscopic-to-macroscopic transition: modulated phases in
4-component DSPC/DOPC/POPC/chol giant unilamellar
vesicles. Biophys. J., 101:L8-L10
This first description of compositionally-controlled Ld + Lo modulated phase behavior.
Heberle FA and Feigenson GW. 2011. Phase separation in lipid
membranes. Cold Spring Harb Perspect Biol., 3:a004630
A review of lipid-lipid interactions with a focus on size of coexisting liquid domains.
Heberle FA, Wu J, Goh SL, Petruzielo RS and Feigenson GW. 2010. Comparison of three ternary lipid bilayer mixtures: FRET and ESR reveal nanodomains. Biophys. J., 99:3309-3318. PMID21081079
These three large scale phase studies, each involving about 2000 samples, show that phase behaviors are remarkably similar among these lipid mixtures, even while phase domain size can be macroscopic or nanoscopic.
Morales-Penningston NF, Wu J, Farkas ER, Goh SL, Konyakhina TM,
Zheng JY, Webb WW and Feigenson GW. 2010. GUV preparation and imaging:
minimizing artifacts. Biochim Biophys Acta., 1798:1324–1332
Light-induced artifacts plague fluorescence microscopic studies. Care is required, particularly the use of low concentrations of dyes (we use 1/5000).
Mills TT, Huang J, Feigenson GW and Nagle JF. 2009. Effects of Cholesterol and Unsaturated DOPC Lipid on Chain Packing of Saturated Gel-Phase DPPC Bilayers. Gen.Physiol.Biophys., 28:126-139
Disagreements in the literature are adressed regarding DPPC mixtures with cholesterol or with DOPC.
Feigenson GW. 2009. Phase diagrams and lipid domains in
multicomponent lipid bilayer mixtures. Biochim Biophys Acta., 1788:47-52
A review of phase behavior of lipid mixtures containing cholesterol.
Mills TT, Toombes GES, Tristram-Nagle T, Heberle FA,
Morales N, Zhao J, Wu J, Toombes GES, Nagle JF and
Feigenson GW. 2008. Order Parameters and Areas in Fluid-Phase
Oriented Lipid Membranes Using Wide Angle X-ray Scattering. Biophys. J., 95:669-681
This study develops a new analytical model to describe acyl chain orientational distribution from WAXS data.
Mills TT, Tristram-Nagle T, Heberle FA, Morales N, Zhao
J, Wu J, Toombes GES, Nagle JF and Feigenson GW. 2008. Liquid-liquid domains in bilayers detected by wide angle x-ray scattering. Biophys. J., 95:682-690
Using a new method to analyze WAXS data, coexisting Ld + Lo domains are detected, even when the domains are nanoscopic.
van Meer G, Voelker DR and Feigenson GW. 2008. Membrane lipids:
where they are and how they behave. Nat Rev Mol Cell Biol., 9:112-124
Lipid compositions and phase behaviors in the different membranes of cells are described.
Zhao J, Wu J, Heberle FA, Mills TT, Klawitter P, Huang G, Costanza G and Feigenson GW. 2007. Phase studies of model biomembranes: Complex behavior of DSPC/DOPC/Cholesterol. Biochim. Biophys. Acta, 1768:2764-2776
FRET, single dye fluorescence, GUV studies, and x-ray diffraction of thousands of different compositions are used to determine phase boundaries for a 3-component mixture.
Zhao J, Wu J, Shao H, Kong F, Jain N, Hunt G and Feigenson GW. 2007. Phase studies of model biomembranes: Macroscopic coexistence of Lα+Lβ, with light-induced coexistence of Lα+Lo Phases. Biochim. Biophys. Acta, 1768:2777-2786
The nature of light-induced macroscopic Ld + Lo phase domains is described.
Feigenson GW. 2007. Phase boundaries and biological membranes. Annu. Rev. Biophys. Biomol. Struct., 36:63–77
A review of the phase behavior of lipid mixtures containing cholesterol, showing that mixtures can be divided into two categories, one type showing macroscopic Ld + Lo phase domains, the other nanoscopic.
Baumgart T, Hunt G, Farkas ER, Webb WW and Feigenson
GW. 2007. Fluorescence probe partitioning between Lo/Ld phases in
lipid membranes. Biochim Biophys Acta., 1768:2182-2194
In DSPC/DOPC/chol, simple examination of fluorescent dye structure is a reliable guide for how the dye partitions between coexisting Ld + Lo phase domains. However, in SM/DOPC/chol the Lo phase has additional constraints in the headgroup region that keep out dyes that contain moieties in this region of the bilayer.
Feigenson GW. 2006. Phase behavior of lipid mixtures. Nature Chemical Biology., 2:560-563
A short review of general principles for connecting studies of model lipid mixtures with the membranes of cells.
Heberle FA, Buboltz JT, Stringer D and Feigenson GW.
2005. Fluorescence Methods to Detect Phase Boundaries in Lipid
Bilayer Mixtures. Biochim. Biophys. Acta, 1746:186-192
A useful primer for how to go from raw fluorescence data to phase boundaries of lipid mixtures.
Buboltz JT and Feigenson GW. 2005. Phospholipid Solubility Determined by Equilibrium Distribution between Surface and Bulk Phases. Langmuir, 21:6296-6301
The aqueous solubility of most biological lipids is so low that it cannot be directly determined. Here we show how to measure DLPC solubility of 25 nM.
Hammond AT, Heberle FA, Baumgart T, Holowka D, Baird B and Feigenson GW. 2005. Crosslinking a Lipid Raft Component Triggers Liquid Ordered–Liquid Disordered Phase Separation in Model Plasma Membranes. Proc. Nat. Acad. Sci. USA, 102:6320-6325
Lipid mixtures containing gangliosidre GM1 are prepared as 1-phase Ld state, but crosslinking the GM1 with cholera toxin B subunits creates coexisting Ld + Lo phase domains.
Shogomori H, Hammond AT, Ostermeyer-Fay AG, Barr DJ, Feigenson GW, London E and Brown DA. 2005. Palmitoylation and intracellular-domain interactions both contribute to raft targeting of linker for activation of T cells (LAT), J. Biol. Chem., 280:18,931-18,942.
Raft targeting of membrane proteins is mysterious. Here we find that acylation of LAT seems insufficient to cause its partition into the Lo phase.
Korlach J, Baumgart T, Webb WW and Feigenson GW. 2005. Detection of motional heterogeneities in lipid bilayer membranes by dual probe fluorescence correlation spectroscopy. Biochim. Biophys. Acta, 1668:158-163
Simultaneous measurement of Dt of a dye that prefers disordered Ld phase and one that prefers ordered Lo phase detects nanoscopic phase coexistence.
Chiang Y-W, Zhao J, Wu J, Shimoyama Y, Freed JH and Feigenson GW. 2005. New method of determining tie-lines in coexisting membrane phases using spin-label ESR. Biochim. Biophys. Acta, 1668:99-105
By collecting and simulating a large number of ESR spectra where Ld + Lβ phases coexist, the field of tielines in the phase region could be determined.
Chiang Y-W, Shimoyama Y, Feigenson GW, and Freed JH. 2004.
Dynamic Molecular Structure of DPPC-DLPC-Cholesterol Ternary Lipid System by Spin-Label Electron Spin Resonance Biophys. J., 87:2483-2496
The order and the dynamics of the different phase regions of this mixture are described.
Tokumasu F, Jin AJ, Feigenson GW and Dvorak JA. 2003. Atomic Force Microscopy of
Nanometric Liposome Adsorption and Nanoscopic Membrane Domain Formation.
When DPPC/DLPC/chol liposomes form a bilayer on mica, AFM shows that the phase behavior is somewhat perturbed, with the adsorption to the substrate favoring the stability of ordered lipd phases.
Tokumasu F, Jin AJ, Feigenson GW and Dvorak JA. 2003. Nanoscopic Lipid Domain
Dynamics Revealed by Atomic Force Microscopy. Biophys. J., 84:2609-2618
AFM reveals some details of the phase domain structure.
Feigenson GW and Buboltz JT. 2001. Ternary Phase Diagram of Dipalmitoyl-PC/dilauroyl-
PC/cholesterol: Nanoscopic Domain Formation Driven by Cholesterol.
Biophys. J., 80:2775-2788
The first well-determined ternary phase diagram of a lipid mixture containing cholesterol is described. This is the very first determination of what has come to be a general type of phase diagram for this class of mixtures, along with the unequivocal finding of nanoscopic domains in this type of mixture.
Buboltz JT and Feigenson GW. 2000. Detection of Coexisting Gel and Fluid Phases by
Equilibrium Surface Pressure Analysis. Langmuir, 16:3606-3611
Although attention to many experimental details is required, measurement of surface pressure at the air/water interface can reveal the phase behavior of lipid bilayer mixtures that are in equilibrium with the monolayer film.
Buboltz JT and Feigenson GW. 1999. A novel strategy for the preparation of liposomes:
rapid solvent exchange. Biochim. Biophys. Acta, 1417:232-245
The widely used method of lipid sample preparation from dry lipid
films is found to yield hydrated bilayer membranes that can have changed composition. Here we report a new method that completely avoids leaving the lipids in the dry film state that causes the artifactual changes in composition.
Huang J and Feigenson GW. 1999. A microscopic interaction model of maximum solubility
of cholesterol in lipid bilayers. Biophys. J., 76:2142-2157
The remarkable finding that cholesterol monohydrate crystals precipitate from lipid-cholesterol bilayers at stoichiometric ratios is shown to depend in a simple way on interactions between lipid neighbors, not on formation of a "condensed complex".
Huang J, Buboltz JT and Feigenson GW. 1999. Maximum solubility of cholesterol in
phosphatidylcholine and phosphatidylethanolamine
bilayers. Biochim.Biophys.Acta, 1417:89-100
The maximum solubility of cholesterol in lipid bilayers is an important thermodynamic parameter, but to find experimentally the true value requires steps that are not so obvious.
Buboltz JT, Huang J and Feigenson GW. 1999. Surface Tension Determination with an
FEP Teflon Rod. Langmuir, 15:5444-5447
Surface tension measurement is potentially a poweful method to examine lipid mixtures, but for such highly insoluble films, the measurement itself can remove enough lipid from the monolayer to give a false reading. We show how to overcome this problem.
Korlach J, Schwille P, Webb WW and Feigenson GW. 1999. Characterization of lipid
bilayer phases by confocal microscopy and fluorescence correlation spectroscopy.
This is the first report that shows how to use fluorescence microscopic imaging of GUVs to identify coexisting lipid phases.
Feigenson GW. 1997. Partitioning of a Fluorescent Phospholipid
Between Fluid Bilayers: Dependence on Host Lipid Acyl Chains,
Biophys. J., 36:3112-3121
The Ld phase has only a small preference among a wide range of PC acyl chain types.