Resveratrol Interaction with Lipid Bilayers: A Synchrotron X-ray Scattering Study

Resveratrol belongs to the large group of biologically active polyphenol compounds, with several beneficial health effects including antioxidant activity, anti-inflammatory action, cardiovascular protection, neuroprotection, and cancer chemoprevention. In the present study, the possibility that the effects of resveratrol described above are caused by resveratrol membrane interactions and structural modifications of lipid bilayers is evaluated. In this context, it is possible that resveratrol interacts selectively with lipid domains present in biological membranes, thereby modulating the localization of the anchored proteins and controlling their intracellular cascades. This study was conducted in a synchrotron particle accelerator, where the influence of resveratrol in the structural organization of lipid domains in bilayers was investigated using small- and wide-angle X-ray scattering (SAXS and WAXS) techniques. Membrane mimetic systems composed of egg l-α-phosphatidylcholine (EPC), cholesterol (CHOL), and sphingomyelin (SM), with different molar ratios, were used to access the effects of resveratrol on the order and structure of the membrane. The results revealed that resveratrol induces phase separation, promoting the formation of lipid domains in EPC, EPC:CHOL [4:1], and EPC:CHOL:SM [1:1:1] bilayers, which brings some structural organization to membranes. Therefore, resveratrol controls lipid packing of bilayers by inducing the organization of lipid rafts. Moreover, the formation of lipid domains is important for modulating the activity of many receptors, transmembrane proteins, and enzymes whose activity depends on the structural organization of the membrane and on the presence or absence of these organized domains. This evidence can thereby explain the therapeutic effects of resveratrol.