Probing the Interaction of Polyphenols with Lipid Bilayers by Solid-State NMR Spectroscopy

Abstract

Polyphenols are bioactive natural products that appear to act against a wide range of pathologies. Mechanisms of activity have not been established, but recent studies have suggested that some polyphenols bind to membranes. We examined the interaction between lipid bilayers and three structurally diverse polyphenols. We hypothesized that features of the polyphenols such as polarity, molecular size, molecular geometry, and number and arrangement of phenol hydroxyl groups would determine the tendency to interact with the bilayer. We examined a mixed polyphenol, (−) epigallocatechin gallate (EGCg); a proanthocyanidin trimer comprising catechin-(4→8)-catechin-(4→8)-catechin (cat3); and a hydrolysable tannin, 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG). These polyphenols were incorporated at different levels into 2H labeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) multi-lamellar vesicles (MLVs). 31P and 2H solid-state NMR experiments were performed to determine the dynamics of the headgroup region and the hydrophobic acyl chain region of the lipid bilayer upon addition of polyphenols. The chemical shift anisotropy (CSA) width of the 31P NMR spectra decreased upon addition of polyphenols. Addition of PGG induces a dramatic reduction on the CSA width compared with the control lipid bilayer sample, while addition of cat3 barely reduces the CSA width. The 2H quadupolar splitting of the lipids also decreased upon addition of polyphenols. At the same concentration, PGG substantially reduced the quadrupolar splitting while cat3 barely reduced it when compared with the control sample. By calculating the order parameters of the acyl chain region of the lipid bilayer, we concluded that the hydrophobic part of the lipid bilayer was perturbed by PGG while cat3 did not cause large perturbations. The data suggest that the polarity of the polyphenols affects the interaction between tannins and membranes. The interactions may relate to the biological activities of polyphenols.

Stability of polyphenols epigallocatechin gallate and pentagalloyl glucose in a simulated digestive system

“…We speculated that polyphenol interaction with lipids could provide stabilization in mixtures with the digestive components. PGG is much more hydrophobic than EGCg, and interacts more strongly with phospholipids than EGCg (Yu, Chu, Hagerman, & Lorigan, 2011), consistent with the stabilization by digestive components we noted for PGG but not for EGCg. Just as interactions with protein may stabilize PGG but decrease its bioavailability, there is some evidence that interactions with amphiphilic molecules might decrease PGG bioavailability.…”

Probing the interaction of Arg9Cys mutated phospholamban with phospholipid bilayers by solid-state NMR spectroscopy

“…2 H quadrupolar splittings of 2 H labels on the entire acyl chain of the POPC-d 31 lipids reflect dynamics of the lipid bilayer hydrophobic region [34, 35, 42], S CD order parameters calculated from the 2 H quadrupolar splittings yield individual 2 HH dynamics along the acyl chain. 2 H nuclei near the membrane surface have larger order parameters than the ones near the membrane core since 2 H nuclei near the membrane surface are more restricted [41].…”

“…Membrane structure and dynamic changes induced by the incorporation of proteins into the phospholipid bilayer can be revealed using 31 P solid-state NMR spectroscopy [33-35]. Also, 2 H solid-state NMR spectroscopy of 2 H labels along the lipid acyl chain can be used to study the dynamics of the hydrophobic region of the membrane [34-42], In this study, interactions between lipid bilayers and WT-PLB, P-PLB and R9C-PLB are investigated from the membrane perspective using 31 P and 2 H solid-state NMR spectroscopy. These experiments shed light onto the loss of functionality of the R9C mutation from the membrane perspective.…”

Effects of hydrolysable tannins on native and artificial biological membranes

“…These substances are also very active. It has been established by now that tannins and catechins are able to affect physical prop erties of cell membranes, regulate cell metabolism [19][20][21][22], link adjacent bilayer surfaces, and induce membrane aggregation [23][24][25]. Interactions of these substances with proteins and lipids were examined in many studies [14,21,25,26].…”

“…Interactions of these substances with proteins and lipids were examined in many studies [14,21,25,26]. It is supposed that these polyphenols can interact electrostatically with hydro philic regions of phospholipids and penetrate into hydrophobic area of a cell membrane causing a decrease of its interphase space from 15 to 5 Å [13,19,23].…”