Effect of Bilayer Partitioning of Curcumin on the Adsorption and Transport of a Cationic Dye Across POPG Liposomes Probed by Second-Harmonic Spectroscopy

Abstract

The effect of Curcumin partitioning into the bilayer during the adsorption and transport of a cationic dye, LDS, across a negatively charged POPG bilayer was investigated by the interface-selective second-harmonic (SH) spectroscopic technique. The intensity of SH electric field (E) arising due to LDS adsorbed on the outer bilayer of the POPG liposome was observed to increase instantaneously (<1 s) following the addition of Curcumin. The fractional increase in the SH electric field (E) and the bilayer transport rates (k) of LDS were studied with respect to the pH of the solution and also with the Curcumin content in the lipid bilayer. Results obtained indicate that compared with the anionic form of the drug, its neutral form is more conducive of increasing the E of LDS. With increasing Curcumin content in the lipid bilayer, two distinct regimes could be observed in terms of E and k values of LDS. For Curcumin:Lipid (C/L) ratio ≤0.02, the E of LDS increases rapidly, while k remains unchanged; and for C/L ratio ≥0.02, the E values remains more or less constant, while there is a significant (∼40 times) increase followed by a modest increase in the k values of LDS. The observed results support an earlier two-state binding model of Curcumin with the POPG bilayer. In addition, it is further proposed that at low C/L ratio Curcumin binds to the surface of the bilayer replacing the counterions (Na) bound to the lipid head groups, which changes the bilayer surface charge density, thereby causing more LDS cations to adsorb on the bilayer surface. At high C/L ratio, Curcumin intercalates within the hydrophobic domain of the bilayer, altering its hydrophobicity and inducing enhanced transport of the LDS cation. Results presented in this work provide further insights into how Curcumin alters bilayer properties when it partitions from the aqueous to the bilayer phase.

Effects of Curcumin on Lipid Membranes: an EPR Spin-label Study

“…Curcumin orientation in the membrane is under debate. Some results suggest that curcumin lies flat on the lipid headgroups, where it forms hydrogen bonds with the lipid molecules [25], whereas some other show that curcumin can penetrate deeply into the membrane and intercalate with the lipid tails [6,9]. According to one of the recent papers, both locations are possible depending on membrane hydration [11].…”

Molecule‐Membrane Interactions in Biological Cells Studied with Second Harmonic Light Scattering

“…It was expected that the rate of transport across the CM should be similar to those obtained from prior liposome‐based studies . In both cases, the molecular probe has to directly diffuse across the lipid bilayer.…”

“…It was expected that the rate of transport across the CM shouldb es imilar to those obtained from prior liposome-based studies. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] In both cases, the molecular probe has to directly diffusea cross the lipid bilayer.S till, the deduced average moleculart ransport rate for the bacterial CM is found to be an order of magnitude slower compared to unilamellar liposomes (ca. 10 À3 s À1 )w hose lipid composition was homogeneous.…”

“…Consequently, the time‐dependent rise and fall of the measured SHS signal is quantitatively related to the molecular densities on the outer and inner surfaces and can be analyzed to reveal the rates of molecular adsorption and transport across the membrane. Following this demonstration, a number of studies have since examined the effects of lipid composition and a variety of environmental factors on the propensity and characteristics of molecular transport across membranes in model liposome systems …”

“…Following this demonstration,anumber of studies have since examined the effects of lipid composition and av ariety of environmental factorso nt he propensity and characteristics of molecular transport across membranes in model liposome systems. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] The studies on liposomes suggested the feasibility that SHS could be used for monitoring molecular transport across membranesi nl iving biological cells. Indeed, in 2010, our laboratory reportedt he first demonstration that SHS could be applied to study molecular transport across membranes in living cells.…”