Curcumin is the active ingredient of the turmeric powder, a natural spice used for generations in traditional medicines. Curcumin's broad spectrum of anti-oxidant, anti-carcinogenic, antimutagenic, and anti-inflammatory properties makes it particularly interesting for the development of pharmaceutical compounds. Due to curcumin's various effects on the function of numerous unrelated membrane proteins, it has been suggested that it affects the properties of the bilayer itself. However, a detailed atomic-level study of the interaction of curcumin with membranes has not been attempted. A combination of solid-state NMR and differential scanning calorimetry experiments shows curcumin has a strong effect on membrane structure at low concentrations. Curcumin inserts deep into the membrane in a transbilayer orientation, anchored by hydrogen bonding to the phosphate group of lipids in a manner analogous to cholesterol. Like cholesterol, curcumin induces segmental ordering in the membrane. Analysis of the concentration dependence of the order parameter profile derived from NMR results suggests curcumin forms higher order oligomeric structures in the membrane that span and likely thin the bilayer. Curcumin promotes the formation of the highly curved inverted hexagonal phase which may influence exocytotic and membrane fusion processes within the cell. The experiments outlined here show promise for understanding the action of other drugs such as capsaicin in which drug-induced alterations of membrane structure have strong pharmacological effects.Turmeric powder prepared from the turmeric plant has been in use for centuries in the traditional medicine of China and India for treating wounds, infections, and other skin problems. 1 The active component of turmeric powder, curcumin (Fig. 1 for the structure of curcumin), has a surprising array of anti-oxidant, anti-cancer, anti-mutagenic, antibiotic, antiviral, anti-fungal, anti-amyloid, anti-diabetic, and anti-inflammatory properties. 2-9 Because of its numerous pharmaceutical effects and its inherent non-toxicity, curcumin has been the focus of many recent biochemical investigations, primarily reporting on its medicinal properties and interactions with specific proteins. Despite intense interest in the physiological effects of curcumin, a general mechanism for its action has not been identified.Studies of curcumin have shown that it influences structurally unrelated membrane proteins across several signaling pathways. 10 For a small minority of these proteins, specific binding of curcumin to the protein has been detected with a binding constant typically in the nanomolar