An interaction of helicid with phosphatidylcholine liposome biomembrane was studied by transmission electron microscopy, UV-vis, fluorescence, Raman and P-31 NMR spectra. The results indicate that most of helicid molecules associate with liposomes at their surface and some of them penetrate the liposomes and locate in the hydrophobic regions of the membrane. The distribution coefficient K-D between liposome phases and aqueous phases is 13.5. The liposome becomes more dispersive and stable in the presence of helicid. The microenvironmental micropolarity and the microhydrophobicity of liposome membrane decrease with the increase of helicid concentration. The interaction of helicid molecules with liposome results in a slight decrease of the membrane longitudinal order, and an increase of the membrane lateral order. A model for the interaction of helicid with liposome biomembrane is proposed on the basis of the change of microenvironment parameters of liposome including the micropolarity, microhydrophobicity and membrane order. The change of microenvironment parameters results mainly from hydrogen bonding interaction between the hydroxyl groups of the pyranoside rings of helicid molecules and the polar head groups of phosphatidylcholine. (C) 2010 Elsevier B.V. All rights reserved.