Interactions of perfluoroalkyl substances with a phospholipid bilayer studied by neutron reflectometry

Nouhi, Shirin; Ahrens, Lutz; Campos-Pereira, Hugo; Hughes, A.; Campana, Mario; Gutfreund, Philipp; Pálsson, Gunnar K.; Vorobiev, Alexeï; Hellsing, Maja S.

doi:10.1016/j.jcis.2017.09.102

Cited by 43 publications

(46 citation statements)

References 52 publications

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“…Therefore, one might wonder what is happening inside the organs. With increasing lipophilicity the PFCs tend more to interact with lipid membranes [ 69 ]. As mentioned above, the PFCs are generally lipophobic, but, e.g., PFOB displays enough lipophilicity to intercalate into the centre of the lipid bilayers of cell membranes up to 2 mol% without causing conformational changes in the membrane (Fig.…”

Section: Pfc-based Oxygen Carriers: Droplets Under Attackmentioning

confidence: 99%

Perfluorocarbon-based oxygen carriers: from physics to physiology

Jägers

Wrobeln

Ferenz

2020

Pflugers Arch - Eur J Physiol

139

108

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Developing biocompatible, synthetic oxygen carriers is a consistently challenging task that researchers have been pursuing for decades. Perfluorocarbons (PFC) are fascinating compounds with a huge capacity to dissolve gases, where the respiratory gases are of special interest for current investigations. Although largely chemically and biologically inert, pure PFCs are not suitable for injection into the vascular system. Extensive research created stable PFC nano-emulsions that avoid (i) fast clearance from the blood and (ii) long organ retention time, which leads to undesired transient side effects. PFC-based oxygen carriers (PFOCs) show a variety of application fields, which are worthwhile to investigate. To understand the difficulties that challenge researchers in creating formulations for clinical applications, this review provides the physical background of PFCs’ properties and then illuminates the reasons for instabilities of PFC emulsions. By linking the unique properties of PFCs and PFOCs to physiology, it elaborates on the response, processing and dysregulation, which the body experiences through intravascular PFOCs. Thereby the reader will receive a scientific and easily comprehensible overview why PFOCs are precious tools for so many diverse application areas from cancer therapeutics to blood substitutes up to organ preservation and diving disease.

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Section: Pfc-based Oxygen Carriers: Droplets Under Attackmentioning

confidence: 99%

Perfluorocarbon-based oxygen carriers: from physics to physiology

Jägers

Wrobeln

Ferenz

2020

Pflugers Arch - Eur J Physiol

139

108

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“…Figure 1C). Given the strict similarity with fatty acids, the likely interaction of PFOA with the lipid bilayer of cell membrane has been previously suggested [28][29][30]. Accordingly, we further evaluated the Given the strict similarity with fatty acids, the likely interaction of PFOA with the lipid bilayer of cell membrane has been previously suggested [28][29][30].…”

Section: Platelets' Membrane Is the Major Cell-accumulation Site Of Bmentioning

confidence: 99%

Increased Cardiovascular Risk Associated with Chemical Sensitivity to Perfluoro–Octanoic Acid: Role of Impaired Platelet Aggregation

Toni

Radu

Šabovic

et al. 2020

IJMS

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Perfluoro–alkyl substances (PFAS), particularly perfluoro–octanoic acid (PFOA), are persisting environmental chemicals showing bioaccumulation in human tissues. Recently, exposure to PFAS has been associated with increased prevalence of cardiovascular diseases (CVDs). However, a causal role of PFAS in atherosclerosis pathogenesis is under-investigated. Here, we investigated the effect of PFOA exposure on platelets’ function, a key player in atherosclerosis process. PFOA accumulation in platelets was evaluated by liquid chromatography-mass spectrometry. Changes in platelets’ membrane fluidity and activation after dose-dependent exposure to PFOA were evaluated by merocyanine 540 (MC540) and anti P-Selectin immune staining at flow cytometry, respectively. Intracellular calcium trafficking was analyzed with Fluo4M probe, time-lapse live imaging. Platelets’ aggregation state was also evaluated with Multiplate® aggregometry analyzer in 48 male subjects living in a specific area of the Veneto region with high PFAS environmental pollution, and compared with 30 low-exposure control subjects. Platelets’ membrane was the major target of PFOA, whose dose-dependent accumulation was associated in turn with increased membrane fluidity, as expected by a computational model; increased activation at resting condition; and both calcium uptake and aggregation upon activation. Finally, exposed subjects had higher serum and platelets levels of PFOA, together with increased aggregation parameters at Multiplate®, compared with controls. These data help to explain the emerging association between PFAS exposure and CVD.

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“… 25 The critical micelle concentration (CMC) of PFHxS, perfluorooctanic acid (PFOA), and perfluorooctanesulfonic acid potassium salt (PFOS) are 18–86, 25–30, and 6.3–8 mM, respectively. 21 , 26 , 27 In order to avoid formation of micelles, the final concentrations of these surfactants employed in this work (<0.5 mM) were much lower than the reported CMC concentrations. Because we have only titrated submM concentrations of the PFCs, the lack of the light-scattering signal on their own is expected.…”

Section: Results and Discussionmentioning

confidence: 95%

“…Studying the interaction of PFCs with liposomes, a model cell membrane, may enable fundamental insights into the mechanism of cytotoxicity. Some previous work has studied the effects of PFCs on cellular lipids, 16 − 21 and some showed that PFCs increased the permeability of cell membranes and altered membrane fluidity. 16 , 17 PFCs also partitioned into membranes, 17 , 18 and PFCs with a longer chain showed a higher tendency to penetrate into the bilayer.…”

Section: Introductionmentioning

confidence: 99%

“… 16 , 17 PFCs also partitioned into membranes, 17 , 18 and PFCs with a longer chain showed a higher tendency to penetrate into the bilayer. 21 The phase transition of 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) liposomes in the presence of PFCs was also studied. 18 , 19 PFCs were found to lower and broaden the phase transition of DPPC membranes, in a way similar to cholesterol.…”

Section: Introductionmentioning

confidence: 99%

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Stabilization of Liposomes by Perfluorinated Compounds

et al. 2018

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Perfluorinated compounds (PFCs) are emerging persistent environmental contaminants that may be toxic to animals and humans. To gain fundamental insights into the mechanism of their toxicity, the interactions of phosphocholine (PC) liposomes as model membranes were studied with three types of PFCs, including perfluorooctanoic acid, perfluorooctane sulfonate, and perfluorohexanesulfonic acid potassium salt, together with three common surfactants: sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and sodium 1-heptanesulfonate (SHS). The interactions were systematically characterized by zeta potential measurement, dynamic light scattering, negative-stain transmission electron microscopy, and fluorescence spectroscopy. Unmodified liposomes, calcein-loaded liposomes, and Laurdan dye-embedded liposomes were all tested. By gradually increasing the temperature, the three PFCs and SHS decreased the leakage of calcein-loaded 1,2-dipalmitoyl-sn-glycero-3-phosphocholine liposomes, whereas SDS and CTAB increased the leakage. The PFCs that affected the lipid membranes stronger than SHS were attributable to their perfluoroalkyl carbon chains. Packing of the lipids was further studied using Laurdan dye as a probe. Calcein leakage tests also indicated that PFCs inhibited lipid membrane leakage induced by inorganic nanoparticles such as silica and gold nanoparticles. This study confirmed the similar effect of the PFCs as cholesterol in affecting membrane properties and would be helpful for understanding the interaction mechanism of PFCs and cell membranes.

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Interactions of perfluoroalkyl substances with a phospholipid bilayer studied by neutron reflectometry

Cited by 43 publications

References 52 publications

Perfluorocarbon-based oxygen carriers: from physics to physiology

Perfluorocarbon-based oxygen carriers: from physics to physiology

Increased Cardiovascular Risk Associated with Chemical Sensitivity to Perfluoro–Octanoic Acid: Role of Impaired Platelet Aggregation

Stabilization of Liposomes by Perfluorinated Compounds

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