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

Abstract

Curcumin is a yellow–orange dye widely used as a spice, food coloring and food preservative. It also exhibits a broad range of therapeutic effects against different disorders such as cancer, diabetes, or neurodegenerative diseases. As a compound insoluble in water curcumin accumulates in cell membranes and due to this location it may indirectly lead to the observed effects by structurally altering the membrane environment. To exert strong structural effects on membrane curcumin needs to adopt a transbilayer orientation. However, there is no agreement in literature as to curcumin’s orientation and its structural effects on membranes. Here, we investigated the effects of curcumin on lipid order, lipid phase transition, and local polarity in a model liposome membranes made of DMPC or DSPC using electron paramagnetic resonance (EPR) spin labeling technique. Curcumin affected lipid order at different depths within the membrane: it slightly increased the phospholipid polar headgroup mobility as monitored by spectral parameters of T-PC, while along the acyl chain the ordering effect was observed in terms of order parameter S. Also, rotational correlation times τ2B and τ2C of 16-PC in the membrane center were increased by curcumin. Polarity measurements performed in frozen suspensions of liposomes revealed enhancement of water penetration by curcumin in the membrane center (16-PC) and in the polar headgroup region (T-PC) while the intermediate positions along the acyl chain (5-PC and 10-PC) were not significantly affected. Curcumin at a lower concentration (5 mol%) shifted the temperature of the DMPC main phase transition to lower values and increased the transition width, and at a higher concentration (10 mol%) abolished the transition completely. The observed effects suggest that curcumin adopts a transbilayer orientation within the membrane and most probably form oligomers of two molecules, each of them spanning the opposite bilayer leaflets. The effects are also discussed in terms of curcumin’s protective activity and compared with those imposed on membranes by other natural dyes known for their protective role, namely polar carotenoids, lutein and zeaxanthin.

Curcumin Accelerates the Lateral Motion of DPPC Membranes

“…Meanwhile, it has also been shown that the protein function is regulated by the properties of the lipid bilayer as a result of the hydrophobic coupling between the protein and the core of the bilayer . These assertions have motivated investigations of the interaction mechanism between curcumin and lipid bilayers. ,− …”

“…Various experimental methods including X-ray diffraction, resonance spectroscopy, and calorimetry have been used to understand the interaction between curcumin and PC lipid bilayers. − Curcumin is a predominantly hydrophobic molecule (Figure ) , that shows a high affinity toward PC membranes. The interaction between curcumin and PC membranes is exothermic and a large partition coefficient (∼10 6 ) is observed. ,, But the position and orientations of curcumin in PC membranes are controversial. − Two different positions of curcumin (i) at the membrane interface, specifically between the membrane head and tail, with its long axis parallel to the plane of the membrane (referred to as surface-associated orientation) and (ii) deeply inserted in the hydrophobic core of the bilayer with its long axis perpendicular to the plane of membrane or transbilayer orientation have been observed. − For example, using nuclear magnetic resonance (NMR) spectroscopy, Barry et al concluded that curcumin has transbilayer orientation in the dimyristoylphosphatidylcholine (DMPC) membrane even at low concentrations. However, using X-ray lamellar diffraction, Huang and co-workers revealed that at low molar concentrations (<3 mol %), curcumin binds at the interface of the 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC) membrane, sitting between the head and the tail, with its long axis parallel to the plane of the membrane.…”

“…Typical length scales on which these motions occur also span a broad range from Angstroms for localized motions to a few micrometers for large-scale cell deformation . Various spectroscopic methods aid in probing these dynamical features including resonance techniques (e.g., NMR and ESR), ,− fluorescence techniques (e.g., fluorescence correlation spectroscopy and fluorescence recovery after photobleaching), , and scattering techniques (dynamic light scattering and quasielastic neutron scattering). ,− Scattering techniques have an edge over the other spectroscopic methods as they can provide both spatial and temporal information about relaxation processes. This is feasible due to an additional variable, the wave vector transfer, Q .…”

Tauroursodeoxycholic Acid (TUDCA)—Lipid Interactions and Antioxidant Properties of TUDCA Studied in Model of Photoreceptor Membranes

“…Higher values of 2Azz indicate higher polarity (lower hydrophobicity) and polarity profiles across the lipid bilayer reflect water penetration into the membrane [ 95 ]. This can be affected by lipid composition, presence of cholesterol, carotenoids, peptides, or drugs [ 94 , 96 , 97 , 98 , 99 ]. Here, we analyzed the effect of TUDCA on polarity profiles across two simple models of membranes containing high and low level of cholesterol ( Figure 6 ).…”

Natural Antioxidant Evaluation: A Review of Detection Methods

“…Usually, carotenoids are located inside cell membranes as highly lipophilic molecules. While strict hydrocarbons, such as lycopene or β-carotene, are arranged exclusively in the inner part of the lipid bilayer, molecules with a more polar configuration containing oxygen atoms attached (like lutein or zeaxanthin) are oriented roughly perpendicular to the membrane surface with their hydrophilic parts oriented to the aqueous environment [ 29 , 30 ].…”