Cholesterol level affects surface charge of lipid membranes in saline solution

Magarkar, Aniket; Dhawan, Vivek; Kallinteri, Paraskevi; Viitala, Tapani; Elmowafy, Mohammed; Róg, Tomasz; Bunker, Alex

doi:10.1038/srep05005

Cited by 175 publications

(148 citation statements)

References 37 publications

(43 reference statements)

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“…However, the binding competitiveness of lipid head groups is diminished by cholesterol contents. As cholesterol concentration increases, the ionic affinity to the membrane decreases, which is in agreement with experiments 19 . When cholesterol concentration [CHOL] ≥ 30%, the ionic binding is significantly reduced.…”

Section: Discussionsupporting

confidence: 79%

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Free energy landscapes of sodium ions bound to DMPC–cholesterol membrane surfaces at infinite dilution

Yang

Bonomi

Calero

et al. 2016

Phys. Chem. Chem. Phys.

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Exploring the free energy landscapes of metal cations on phospholipid membrane surfaces is important for the understanding of chemical and biological processes in cellular environments. Using metadynamics simulations we have performed systematic free energy calculations of sodium cations bound to DMPC phospholipid membranes with cholesterol concentration varying between 0% (cholesterol-free) and 50% (cholesterol-rich) at infinite dilution. The resulting free energy landscapes reveal the competition between binding of sodium to water and to lipid head groups. Moreover, the binding competitiveness of lipid head groups is diminished by cholesterol contents. As cholesterol concentration increases, the ionic affinity to membranes decreases. When cholesterol concentration is greater than 30%, the ionic binding is significantly reduced, which coincides with the phase transition point of DMPC-cholesterol membranes from a liquid-disordered phase to a liquid-ordered phase. We have also evaluated the contributions of different lipid head groups to the binding free energy separately. The DMPC's carbonyl group is the most favorable binding site for sodium, followed by DMPC's phosphate group and then the hydroxyl group of cholesterol.

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Section: Discussionsupporting

confidence: 79%

“…Na + is considered bound to the membrane for CLP > 0 and unbound for CLP = 0. 19 . Although our results are strictly valid only at infinite ion dilution, a similar behavior should be expected at moderate ion concentrations, where ion-ion correlations are not important 44 .…”

Section: Resultsmentioning

confidence: 99%

Free energy landscapes of sodium ions bound to DMPC–cholesterol membrane surfaces at infinite dilution

Yang

Bonomi

Calero

et al. 2016

Phys. Chem. Chem. Phys.

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show abstract

“…3B). CLR is an important structural component of cellular membranes and exerts profound effects on membrane physical properties [21,23,42]. It is conceivable that tissue’s ability to accumulate CLR may be limited by the membrane physical properties required for life as we know it.…”

Section: Discussionmentioning

confidence: 99%

Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle

Simakova

Bisen

Dopico

et al. 2017

Biochemical Pharmacology

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Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10 mg/kg daily for 18–23 weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60 mmHg and AICAC was evoked by 50 mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR + atorvastatin group but not in high CLR diet + placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet + atorvastatin group when compared to high CLR diet + placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin’s ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism.

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“…Cholesterol is the main component added in the liposomal formulations to stabilize the bilayer of liposomes (Laouini et al 2012;Magarkar et al 2014). Depending upon the rigidity and fluidity of bilayer, the molar percentage of cholesterol varies from 30-45% of total liposomes components ( Kirby and Gregoriadis 1980;Laouini et al 2012) as it provides membrane fluidity, elasticity, permeability and stability to liposomes (Kirby and Gregoriadis 1980;Magarkar et al 2014).…”

Section: Cholesterolmentioning

confidence: 99%