Effect of Phloretin on the Dipole Potential of Phosphatidylcholine, Phosphatidylethanolamine, and Phosphatidylglycerol Monolayers

Abstract

The effect of phloretin on the potential of phosphatidylcholine (PC), phosphatidylethanolamine (PE,) and phosphatidylglycerol (PG) monolayers below and above the phase transition in mixtures of different PC/PE ratios with and without cholesterol of ester and ether phospholipids have been determined. The effectiveness of phloretin to decrease the dipole potential of monolayers in the fluid state is lessened by the moieties esterified to the phosphate group in the sequence choline > ethanolamine > glycerol. These effects on the dipole potential of monolayers are independent of the presence of carbonyls. In addition, in the gel state phloretin does not affect the dipole potential on dimyristoylphosphatidylethanolamine, although it is very pronounced in dimyristoylphosphatidylcholine. The changes of the dipole potential induced by phloretin were correlated with the packing of the lipids and with the formation of intermolecular hydrogen bonds between adjacent phospholipid molecules. These results may be indicative of the different distribution of polarized water around the phosphate groups imposed by the surrounding environment.

The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

“…This tendency is related, at least in part, to the lipid shape (as is intuitive); for example, large headgroups and short tails normally increase the propensity to curl away from the water phase (forming for example micellar structures), whereas small headgroups and long tails tend to increase the desire to bend towards the water phase (forming “inverse” phases). Regarding the dipole potential, its experimental estimate [86], [87] could be reproduced by adjusting the magnitude of the glycerol and ester point dipoles, and the rigidity of the dipole orientation-restraining potential (equation 10).…”

Effect of Phloretin on the Binding of 1-Anilino-8-naphtalene sulfonate (ANS) to 1,2-Dimyristoyl-sn-glycero-3-phosphocoline (DMPC) Vesicles in the Gel and Liquid-Crystalline State

“…It has been shown that the decrease by phloretin of the dipole potential in phosphatidylcholine (PC) monolayers is more significant in the less hydrated gel state than in fluid state. This effect was attributed to neutralization or reorientation of dipole moieties at the interface others that the acyl chain carbonyl groups, since results obtained with ether-linked DMPC were similar to those obtained with esther-linked DMPC (Lairion and Disalvo 2004). More recently, Efimova and Ostroumova (2012) studied the effect of phloretin and other dipole modifiers on the magnitude of the dipole potential of planar bilayers composed by different phospholipid and sterols mixtures at room temperature.…”

“…At higher cholesterol concentrations, the capability of the sterol of promoting a liquid-ordered phase would decrease the effectiveness of phloretin as dipole potential modifier as a consequence of a reduced possibility of formation of hydrogen bonds between hydroxyls of phloretin and the phospholipids' P=O group (Ostroumova et al 2013). It has also been reported (Lairion and Disalvo 2004) that phloretin is more effective in reducing the dipole potential of DMPC monolayers in gel phase (from 515 to 270 mV) than in the liquid phase (from 449 to 297 mV). The increase in the affinity of DMPC and DPPC LUVs in the gel phase for ANS reported here can be explained by postulating that phloretin simply adsorbs to bilayers in the gel phase as it does to monolayers at high surface pressures (Cseh and Benz 1999).…”

“…Such structural changes would result in: (i) decrease in the number of ANS ''binding sites;'' (ii) increase of the polarity of the ANS ''binding sites'' with the concomitant decrease in the fluorescence lifetime of the bound ANS and increase of the intrinsic ANS K d . Phloretin also reduce the dipole potential in liquid-crystalline phases (Lairion and Disalvo 2004). Therefore, two opposite effects of phloretin regarding the apparent ANS dissociation constant must be considered: (i) an increase of the intrinsic dissociation constant; and (ii) a reduction of the dipole potential and consequently the density of negative surface charges.…”

“…Phloretin (among other chalcones and flavonols) decreased the dipole potential of phospholipid-and sterol-containing membranes. The presence of cholesterol strongly influenced the magnitude of phloretin's effect (Lairion and Disalvo 2004;Efimova and Ostroumova 2012;Ostroumova et al 2013). …”