The biophysical interaction of ferulic acid with liposomes as biological membrane model: The effect of the lipid bilayer composition

Molecules able to prevent lipid peroxidation have attracted attention due to their potential to act against lipid peroxidation-induced disorders including cancer and neurological diseases, such as Alzheimer's disease. Ferulic acid (FA) is a phenolic compound with antioxidant properties but in vivo evidence remains limited. Since the interaction of drugs with biological membranes plays a key role on their therapeutic activity, the biophysical interaction between FA and mimetic cell membrane models was addressed in this study. Liposomes with increasing levels of complexity composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), DMPC:cholesterol (CHOL) [85:15] and DMPC:CHOL:sphingomyelin (SM) [75:15:10] were used as in vitro biomembrane models. Electrophoretic light scattering technique was used to assess the effect of FA on the membrane surface charge. Derivative UV-Vis spectrophotometry, dynamic light scattering, and fluorescence quenching were the techniques chosen to determine the FA's partition into the bilayer, the effect of FA on membrane fluidity and the location of FA within the membrane, respectively. The results suggest that FA is located near to the membranes' surface interacting electrostatically with the zwitterionic polar heads of phospholipids. Also, the FA's affinity to the models is highly dependent on the lipid composition, with a significant reduction of FA's partition with the increase of the membranes' complexity. As consequence, FA only affected the membrane fluidity of the simplest model (DMPC) by increasing its rigidity, with no effect observed in rigid membranes (DMPC:CHOL and DMPC: CHOL:SM). Thus, the results indicate that the FA-membrane interactions depend on the lipid composition, complexity, and physical state of membranes. (C) 2020 Elsevier B.V. All rights reserved.