Spontaneously formed mixed vesicles were prepared with n-dodecylbetaine and the ammonium salt of perfluoropolyether carboxylate, and they were loaded with the water-soluble beef heart cytochrome c. The resulting dispersions were characterized with Light and neutron scattering patterns, UV-vis spectra, and magnetic resonances (NMR and ESR). Proteins-containing vesicles showed scattering patterns that were interpreted in terms of a decrease of the membrane curvature with a resultant increase of the vesicle size that ranged from 83 to 113 nm, depending on the cytochrome c concentration in the dispersion. The interactions between surfaces of protein and of vesicle membrane, which could be responsible for the decreased curvature, did not alter either the optical properties of the heme unit of the protein (from UV-vis) or the dynamics of the vesicle membrane (from H-1 NMR of betaine and ESR of membrane-soluble doxylstearic acids). Cytochrome c was therefore suggested to be surrounded by a shell of water according to the so-called water-shell model. A comparison was made with the behavior of hydrophobic porphyrins introduced in the same vesicle system, as previously reported from the authors.