Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine

Yesylevskyy, Semen O.; Rivel, Timothée; Ramseyer, Christophe

doi:10.1101/602177

Cited by 13 publications

(15 citation statements)

References 28 publications

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“…Numerous studies show that there are many substances, interfacially active peptides [55][56][57] and non-peptide compounds that can influence membrane curvature, and vice versa. Yesylevskyy and colleagues have shown that the permeability of the model lipid membrane for cisplatin and gemcitabine depends on the curvature [58]. Barry and colleagues showed that curcumin, a lipophilic drug, binds to dimyristoyl-phosphocholine (DMPC) with a transbilayer orientation, anchoring to the bilayer by a hydrogen bond to the phosphate group, while, in dipalmitoleoyl-glycero-phosphoethanolamine (DiPOPE) vesicles, it promotes and stabilizes the formation of the inverted hexagonal (HII) phase.…”

Section: Discussionmentioning

confidence: 99%

Study of Resveratrol’s Interaction with Planar Lipid Models: Insights into Its Location in Lipid Bilayers

Meleleo

2021

Membranes

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Resveratrol, a polyphenolic molecule found in edible fruits and vegetables, shows a wide range of beneficial effects on human health, including anti-microbial, anti-inflammatory, anti-cancer, and anti-aging properties. Due to its poor water solubility and high liposome-water partition coefficient, the biomembrane seems to be the main target of resveratrol, although the mode of interaction with membrane lipids and its location within the cell membrane are still unclear. In this study, using electrophysiological measurements, we study the interaction of resveratrol with planar lipid membranes (PLMs) of different composition. We found that resveratrol incorporates into palmitoyl-oleoyl-phosphatidylcholine (POPC) and POPC:Ch PLMs and forms conductive units unlike those found in dioleoyl-phosphatidylserine (DOPS):dioleoyl-phosphatidylethanolamine (DOPE) PLMs. The variation of the biophysical parameters of PLMs in the presence of resveratrol provides information on its location within a lipid double layer, thus contributing to an understanding of its mechanism of action.

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Section: Discussionmentioning

confidence: 99%

Study of Resveratrol’s Interaction with Planar Lipid Models: Insights into Its Location in Lipid Bilayers

Meleleo

2021

Membranes

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“…Food and Drug Administration. 3,4 Since then, an impressive amount of experimental 3,[5][6][7][8][9][10][11] and theoretical [12][13][14][15][16][17] work has been carried out to elucidate the mechanism of action of cisplatin, which is widely employed as chemotherapeutic drug in the treatment of patients with bladder, ovarian, head and neck, lung, testicular, cervical, esophageal, breast and brain cancers. 18 Moreover, the success shown by cisplatin motivates the design and investigation of many other platinum-based compounds with improved biophysiological properties in the last decades.…”

Section: Introductionmentioning

confidence: 99%

The Permeation Mechanism of Cisplatin through a Dioleoylphosphocholine Bilayer

Ruano¹,

Cárdenas²,

Nogueira

2021

Preprint

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The investigation of the intermolecular interactions between platinum-based anticancer drugs and lipid bilayers is of special relevance to unveil the mechanisms involved in different steps of the anticancer mode of action of these drugs. We have simulated the permeation of cisplatin through a model membrane composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine lipids by means of umbrella sampling classical molecular dynamics simulations. The initial physisorption of cisplatin into the polar region of the lipid membrane is controlled, in a first moment, by long-range electrostatic interactions with the choline groups and, in a second step, by long-range electrostatic and hydrogen bond interactions with the phosphate groups. The second half of the permeation pathway, in which cisplatin diffuses through the nonpolar region of the bilayer, is characterized by the drop of the interactions with the polar heads and the rise of attractive interactions with the non-polar tails, which are dominated by van der Waals contributions.

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“…Interestingly, a recent study showed that positive (convex) and negative (concave) curvature increases water permeability on an asymmetric composition mimicking the plasma membrane. 65 Positive curvature implies that the polar heads get further apart which creates packing defects 66 facilitating water entry into the membrane. For negative curvature, it is less clear why water permeability is enhanced compared to a flat membrane.…”

Section: Simulations Of Dopc Membranes Under a Directional Pressurementioning

confidence: 99%

Molecular Study of Ultrasound-Triggered Release of Fluorescein from Liposomes

et al. 2021

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Several investigations have suggested that ultrasound triggers the release of drugs encapsulated into liposomes at acoustic pressures low enough to avoid cavitation or high hyperthermia. However, the mechanism leading to this triggered release as well as the adequate composition of the liposome membrane remain unknown. Here, we investigate the ultrasound triggered release of fluorescein disodium salt encapsulated into liposomes made of 1,2-dioleoyl-sn-glycero-3-phosphocholi (DOPC) or 1,2-distearoylphosphatidylethanolamie (DSPC) lipids with various concentrations of cholesterol (from 0 to 44 mol%).The passive release of encapsulated fluorescein was first characterized. It was observed to be higher when the membrane is in a fluid phase and increased with temperature but decreased upon addition of cholesterol. Next, the release of fluorescein was measured at 1 different acoustic frequencies (0.8, 1.1, 3.3 MHz) and peak-to-peak pressures (0, 2, 2.5, 5, 8 MPa). Measurements were performed at temperatures where DOPC and DSPC liposomes were respectively in the fluid or gel phase. We found that the release rate did not depend on the ultrasound frequency. For DOPC liposomes, the ultrasoundtriggered release of fluorescein decreased with increasing concentration of cholesterol in liposomes, while the behavior was more complex for DSPC liposomes. Overall, the triggered release from DSPC liposomes was up to ten times less than DOPC liposomes.Molecular dynamics simulations performed on a pure DOPC membrane showed that a membrane experiences, under a directional pressure of ±2.4 MPa, various changes in properties such as the area per lipid (APL). An increase in APL was notably observed when the simulation box was laterally stretched or perpendicularly compressed, which was accompanied by an increase in the number of water molecules crossing the membrane. This suggests that ultrasound most probably enhances the diffusion of encapsulated molecules at small acoustic pressures by increasing the distance between lipids.

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Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine

Cited by 13 publications

References 28 publications

Study of Resveratrol’s Interaction with Planar Lipid Models: Insights into Its Location in Lipid Bilayers

Study of Resveratrol’s Interaction with Planar Lipid Models: Insights into Its Location in Lipid Bilayers

The Permeation Mechanism of Cisplatin through a Dioleoylphosphocholine Bilayer

Molecular Study of Ultrasound-Triggered Release of Fluorescein from Liposomes

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