Cholesterol Partition and Condensing Effect in Phase-Separated Ternary Mixture Lipid Multilayers

Abstract

The cholesterol partitioning and condensing effect in the liquid-ordered (Lo) and liquid-disordered (Ld) phases were systematically investigated for ternary mixture lipid multilayers consisting of 1:1 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-phosphocholine with varying concentrations of cholesterol. X-ray lamellar diffraction was used to deduce the electron density profiles of each phase. The cholesterol concentration in each phase was quantified by fitting of the electron density profiles with a newly invented basic lipid profile scaling method that minimizes the number of fitting parameters. The obtained cholesterol concentration in each phase versus total cholesterol concentration in the sample increases linearly for both phases. The condensing effect of cholesterol in ternary lipid mixtures was evaluated in terms of phosphate-to-phosphate distances, which together with the estimated cholesterol concentration in each phase was converted into an average area per molecule. In addition, the cholesterol position was determined to a precision of (±0.7Å) and an increase of disorder in the lipid packing in the Lo phase was observed for total cholesterol concentration of 20∼30%.

Imaging non-classical mechanical responses of lipid membranes using molecular rotors

“…6 . This observation is consistent with cholesterol partitioning in the L d phase, 70 and in agreement with the observed lifetimes of 1 in DOPC : cholesterol LUVs (Fig. S5 † ).…”

“…This could be due to the increased fraction of cholesterol partitioning in the DOPC rich phase. 70 The increase in viscosity under compression could be compared to that in 40 : 40 : 20 GUVs. As stress is released by fission of membrane buds, the curvature-induced softening of the more ordered L o phase is not triggered and, instead, an increase of the overall viscosity due to compression of the unsaturated lipid chains is observed.…”

Membrane Remodeling by Arc/Arg3.1

“…Lipid rafts have also been classified as liquid-ordered (L o ) membrane domains, in contrast to the more fluid liquid-disordered (L d ) domains which are enriched in unsaturated lipids ( Bieberich, 2018 ). To test whether Arc-dependent vesicle formation occurs preferentially from L d or L o domains, LAURDAN-labeled GUVs were prepared from a ternary lipid mixture of DOPC, DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and cholesterol at a 1:1:1 ratio, which allows the separation of liquid phases ( Ma et al, 2016 ). LAURDAN is one of the family of 2,6-naphthalene modified probes designed by Weber ( Weber and Farris, 1979 ) to be sensitive to the polarity of its environment.…”

Properties of Artificial Phospholipid Membranes Containing Lauryl Gallate or Cholesterol

“…The solubility limit of cholesterol in the DOPC multilayers is 40 mol% (Hung et al 2007 ). The condensing effect for the DPPC-rich liquid-ordered L o phase is stronger than for the DOPC-rich liquid-disordered L d phase (McConnell and Radhakrishnan 2003 ; Ma et al 2016 ). Ma et al proved that Chol accumulates in a larger amount in the DPPC-stabilizing L o phase within the L d matrix phase.…”

“…Ma et al proved that Chol accumulates in a larger amount in the DPPC-stabilizing L o phase within the L d matrix phase. Cholesterol increases the electron density in the lipid-chain region in the DPPC-rich phase more than in the DOPC-rich phase (Ma et al 2016 ). For equal mole fractions of DPPC and DOPC and 20% Chol at 25 °C, partition of Chol into the L o and L d phases is 31% and 10–11%, respectively.…”