The morphology and stability of small unilamellar egg yolk phosphatidylcholine (EggPC) liposomes modified with the Pluronic (R) copolymer (poly (oxyethylene)-poly (oxypropylene)-poly (oxyethylene) (PEO-PPO-PEO)) with different compositions on mica surface have been investigated using atomic force microscopy. Morphology studies reveal significant morphological changes of liposomes upon incorporating the Pluronic (R) copolymer. Bilayers are observed for Pluronic (R) with small hydrophilic (PEO) chain lengths such as L81 [(PEO)(2)(PPO)(40)(PEO)(2)] and L121 [(PEO)(4)(PPO)(60)(PEO)(4)]; bilayer and vesicle coexistence is observed for P85 [(PEO)(26)(PPO)(39.5) (PEO)(26)] and F87 [(PEO)(61.1)(PPO)(39.7)(PEO)(61).(1)]; and stable vesicles are observed for F88 [(PEO)(103.5)(PPO)(39.2)(PEO)(103.5)], F127 [(PEO)(100)(PPO)(65)(PEO)(100)], and F108 [(PEO)(132.6)(PPO)(50.3)(PEO)(132.6)]. The micromechanical properties of Pluronic (R)-modified EggPC vesicles were studied by analyzing AFM approaching force curve. The bending modulus (k(c)) of the Pluronic (R)-modified EggPC vesicles increased several-fold compared with that of the pure EggPC vesicles. The significant difference is due to the enhanced rigidity of the EggPC vesicles as a result of the incorporation of PPO molecules and PEO chains. Based on the analysis of onset point by AFM and diameters of vesicles by light scattering, it was concluded that the favorable model to describe the polymer-bilayer interaction is the membrane-spanning model. (c) 2004 Elsevier Inc. All rights reserved.