Fully atomistic molecular dynamics modeling of photoswitchable azo-PC lipid bilayers: structure, mechanical properties, and drug permeation

Phospholipid based vesicles called liposomes are commonly used as packaging in advanced drug delivery applications. Stimuli-responsive liposomes have been designed to release their contents under certain conditions, for example through heating or illumination. However, in the case of photosensitive liposomes based on azo-PC, namely phosphatidylcholine lipids with azobenzene incorporated into one of the two lipid tails, the release mechanism is not known. Here we show, using fully-atomistic molecular dynamics simulations of pure azo-PC bilayers, that drug permeation through the bilayer is driven by a light-induced gel-to-liquid lipid phase transition that softens the membrane bending rigidity by an order of magnitude, increases the area per lipid, and decreases the membrane thickness. Furthermore, using phenol as a model drug, we quantified its translocation free energy and its ability to cross the bilayer as a result of a chemical potential gradient induced through a double-bilayer simulation unit cell. The molecular level structural and dynamic information obtained in this study should be of help in designing new azo-PC based liposomes.