α-tocopherol (αtoc; vitamin E) is an essential nutrient sufficiently acquired through a balanced diet. This fat-soluble vitamin is most known for its antioxidative properties; however, its fundamental mechanism of action in cellular membranes remains unknown. To this end, we use time-resolved small-angle neutron scattering and a contrast matching scheme to determine the intervesicular exchange (k) and intrabilayer flip-flop (k) rates of αtoc in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine vesicles. Moreover, we investigate the role of vesicle concentration and various types of cyclodextrins in affecting these rates. For a 25 mg/mL sample concentration, it was determined that k and k were 1.35 ± 0.03 × 10 and 0.54 ± 0.10 × 10 min, which represent half-lives of 513.4 ± 11.7 and 1285.1 ± 242.7 min, respectively. Differential scanning calorimetry confirmed the observed timescales of αtoc movement.
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