Correlating mono- and bilayers of lipids to investigate the pronounced effects of steroid hormone 17α-ethynylestradiol on membrane models of DPPC/cholesterol

Abstract

Risks to human health have been reported owing to prolonged exposure to hormones, whose action depends on their molecular-level interaction with cell membranes. In this study, we investigate the interaction of the synthetic hormone 17 α-ethynylestradiol (EE2) in two different membrane models, Langmuir monolayers and giant unilamellar vesicles (GUVs) made with a binary mixture of 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) and cholesterol (Chol) in order to mimic the plasma membrane of mammalian cells. EE2 was found to expand the Langmuir monolayers, with shifts to larger areas per molecule in the surface pressure isotherm. In all of these observations, stronger effects were noted for the DPPC/Chol monolayers with XChol = 0.3, which mimics the proportion of phospholipid/sterol in the plasma membrane. At high surface pressures, EE2 is believed to weaken the attractive interactions between DPPC and Chol, in addition to affecting the ordering of the lipid chains as indicated in polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) measurements. In GUVs obtained with XChol = 0.3 mixtures, EE2 induced a phase contrast loss as a result of increased permeability of the lipid bilayer. The results with Langmuir monolayers and GUV combined point to EE2 action on representative cell membranes, which can be correlated with physiological effects caused by indirect intake of EE2.