Characterizing the embedded states of a fluorescent probe within a lipid bilayer using molecular dynamics simulations

The physicochemical properties of lipid bilayers (membranes) are closely associated with various cellular functions and are often evaluated using absorption and fluorescence spectroscopies. For instance, by employing fluorescent probes that exhibit spectra reflective of the surrounding membrane environment, one can estimate the membrane polarity. Thus, elucidating how such probes are embedded within the membranes would be beneficial for enabling a deeper interpretation of the spectra. Here, we apply molecular dynamics simulation with an enhanced sampling method to investigate the embedded state of 6-propionyl-2-dimethylaminonaphthalene (Prodan) within a membrane composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine, as well as its variation upon the addition of ethanol as a cosolvent to the aqueous phase. In the absence of ethanol, it is found that the bulky moieties of Prodan (propionyl and dimethylamine groups) prefer to be oriented toward the membrane center owing to the voids existing near the center. The structural change in the membrane induced by the addition of ethanol causes a reduction in the void population near the center, resulting in a diminished orientation preference of Prodan.