yThe interactions between a random copolymer of N-isopropylacrylamide (NIPAM), N-[4-(1-pyrenyl)-butyl]-N-n-octadeclacrylamide, and N-glycylacrylamide (Gly) (PNIPAM-Py-Gly) with a series of vesicles have been examined by fluorescence spectroscopy, centrifugation assays, and capillary electrophoresis. The copolymer exhibits pH-sensitivity due to the carboxylic acid group of the glycine residues (15 mol %), thermosensitivity due to the NIPAM I residues (84 mol %), and amphiphilic characteristics due to the pyrenyl octadecyl moieties (1 mol Sc). In the presence of salts, complex formation was detected between the copolymer and cationic or anionic nonphospholipid liposomes based on the nonionic surfactant n-octadecyldiethylene oxide ((EO)(2)C18H37) and cationic phospholipid liposomes. Weak interaction was detected between the copolymer and neutral phospholipid liposomes under the same conditions. The effects of the charge density of the liposomes and the lipid concentration on the copolymer/liposome interactions were examined as a function of pH and temperature. The binding of the copolymer to the liposomes is shown to be controlled primarily through hydrogen bond formation between the hydroxyl groups of the (EO)(2)C18H37 and the amide groups of the NIPAM residues, through electrostatic interactions between the charged surfactants of the bilayer and the glycine residues, and, a lesser extent, by hydrophobic forces.