Phase behavior of a binary lipid system containing long- and short-chain phosphatidylcholines

Abstract

Bilayered micelles, or so-called bicelles, are generally made of long-and short-chain lipids. They are extensively used as model membranes to study the structure of membrane-associated peptides or proteins and their interactions with membranes. However, the phase behavior of lipid mixtures composed of longand short-chain lipids, especially at low temperatures, is still not very clear. In this work, the most commonly used long-chain lipid, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and a short-chain lipid, 1,2-dioctanoyl-sn-glycero-3-phosphocholine (diC8PC), were selected as a bicellar model to study their phase behavior. Over the whole range of DPPC/diC8PC molar ratios (q) studied in this work, a lamellar crystalline phase (L c 0 ) enriched in DPPC was found to be the most stable phase at 5 C, together with a diC8PC-enriched micelle phase. Interestingly, a metastable phase, named the U phase in this work, was observed in the mixtures with a DPPC/diC8PC molar ratio between 1 and 4. The metastable U phase was found to be lacking in long-range order in the direction of the bilayer surface normal, but bearing a different "crystalline phase-like" hydrocarbon chain packing mode, in comparison with the lamellar crystalline phase. The kinetic properties of the U phase were also studied in detail, and it was found that the phase acts as a precursor phase in the process of forming the most stable crystalline phase. This work deepens our understanding of lipid crystallization behavior, and is also a step forward towards a more detailed picture of the phase behavior of lipid mixtures composed of long-and short-chain lipids.

Spontaneous Membrane Nanodomain Formation in the Absence or Presence of the Neurotransmitter Serotonin

“…Further experimental evidence for small nanodomains was collected applying Förster resonance energy transfer (FRET) to model membranes (De Almeida et al, 2005;Petruzielo et al, 2013;Koukalová et al, 2017). Other nanoscopic information on membrane domains was achieved using X-ray scattering (SAXS, WAXS) (Sun et al, 2017), neutron scattering (SANS, QENS) (Pencer et al, 2007), or 2 H NMR (Veatch et al, 2007;Bartels et al, 2008;Bunge et al, 2008;Engberg et al, 2016;Bosse et al, 2019). However, while nanometer spatial resolution could be collected for a number of different model membrane compositions (see Cebecauer et al, 2018 for a comprehensive review), the sub-microsecond and typically as well sub-millisecond dynamics is masked by the limited temporal resolution of the above advanced microscopy techniques, or relies on model assumptions.…”

Fabrication of Asymmetric Phosphatidylserine-Containing Lipid Vesicles: A Study on the Effects of Size, Temperature, and Lipid Composition

“…The super stability of the vesicles can be understood by the flip-flop properties of the lipids in membranes. Generally, a lipid species shows a low flip-flop rate at low temperatures, especially below its main phase transition temperature ( T m ). ,,, Thus, DPPC in the vesicles would keep a low flip-flop rate at room or lower temperatures as its T m is about 41 °C. , According to the study from Marquardt et al, the flip-flop rate constant of DPPC at 20 °C is less than 3.06 × 10 –4 h –1 . Although DOPS has a low T m (−11 °C), the low flip-flop rates of PC lipids would impose a steady distribution of DOPS in the two leaflets because its net transfer needs DPPC molecules to make space.…”

Regimes of Complex Lipid Bilayer Phases Induced by Cholesterol Concentration in MD Simulation

“…However, in the MARTINI model, the T m of DPPC has been determined to be as low as 292.4 K-as determined via the generalized replica-exchange MD method (78)-and 296 K as determined via conventional replica-exchange MD (79). Additionally, binary mixtures of DPPC with other lipids are known to both substantially decrease T m and broaden the corresponding peak in the heat capacity (52)(53)(54). For example, in an equimolar DPPC:DOPA mixture, T m decreases to $294.45 5 0.2 K (54).…”

“…At relatively lower T (or higher T m ), the S o phase is evidenced to exist as a macroscopic phase-separated state via fluorescence experiments, AFM, and NMR. The S o phase can disappear at physiological temperatures because of the presence of Chol (11,(48)(49)(50)(51) or unsaturated lipids (52)(53)(54)(55), which lower the T m of saturated lipids. At high (T40 mol%) Chol concentrations, macroscopic phase separations disappear.…”