Determining the Rates of α-Tocopherol Movement in DPPC Vesicles Using Small Angle Neutron Scattering

Biophys J. 2025 Jan 17:S0006-3495(25)00021-9. doi: 10.1016/j.bpj.2025.01.008. Online ahead of print.

Abstract

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 (TR-SANS) and a contrast matching scheme to determine intervesicular exchange (kex) and intrabilayer flip-flop (kf) rates of αtoc in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) vesicles. Moreover, we investigate the role of vesicle concentration and various types of cyclodextrins in affecting these rates. For the 25 mg/mL sample concentration it was determined that kex and kf were 1.35 ± 0.03 x 10-3 min-1 and 0.54 ± 0.10 x 10-3 min-1, which represent half-lives (T1/2) of 513.4 ± 11.7 min and 1285.1 ± 242.7 min, respectively. Differential scanning calorimetry confirmed the observed timescales of αtoc movement.