Cholesterol modulates the interaction between paclitaxel and Langmuir monolayers simulating cell membranes

The composition of Langmuir monolayers used as cell membrane models is an essential factor for the interaction with biologically-relevant molecules, including pharmaceutical drugs. In this paper, we report the modulation of effects from the antineoplastic drug paclitaxel by the relative concentration of cholesterol in the Langmuir monolayers of ternary mixtures of dipalmitoylphosphatidylcholine, sphingomyelin, and cholesterol. Since the dependence on cholesterol concentration for these monolayers simulating lipid rafts is non-monotonic, we analyzed the surface pressure and compressibility modulus data with the multidimensional projection technique referred to as interactive document mapping (IDMAP). The maximum expansion induced by paclitaxel in surface pressure isotherms was observed for 27% cholesterol, while the compressibility modulus decreased most strongly for the monolayer with 48% cholesterol. Therefore, the physiological action of paclitaxel may vary depending on whether it is associated with penetration in the membrane or with changes in the membrane elasticity.

Automated summary

The composition of Langmuir monolayers, specifically the relative concentration of cholesterol, plays a crucial role in modulating the effects of the antineoplastic drug paclitaxel. The dependence on cholesterol concentration for these monolayers simulating lipid rafts is non-monotonic, affecting surface pressure and compressibility modulus differently. The physiological action of paclitaxel may vary depending on its interaction with membrane penetration or membrane elasticity changes.