Ability to grow nanomaterials in different sizes, shapes and functionalities with exceptional control has catalyzed significant advances in nanomedicine, diagnosis and treatment of diseases. The interaction of nanoparticles (NPs) with cell membranes effectively alters certain physical properties such as fluidity, elasticity, flexibility, and permeability of cell membranes. Herein, we constructed various vesicle systems using dimyristoyl phosphatidylcholine (DMPC), a zwitterionic phospholipid molecule widely used for model cell membranes. In some experiments, DMPC vesicles were doped with cholesterol to modulate the membrane integrity. Vesicles were then treated with colloidal gold or silver nanoparticles (AuNPs/AgNPs) at various sizes and concentrations for further examination and analysis with fluorescence spectroscopy, fluorescence microscopy, atomic force microscopy (AFM), as well as hyperspectral dark-field microscopy. Our data suggest that AuNPs cause localized stiffening in the membranes whereas fluidization in the long range. AuNPs were found to interact with vesicles in a different way than AgNPs do. What we learned in this work provides better understanding on the mechanisms of AuNP/AgNP and membrane interactions for their respective future applications in nanomedicine and nanotechnology.