To investigate the behavior of plasma Polymers in biomaterial applications, we studied plasma polymerized hexane (ppHex) and plasma polymerized allylamine (ppAAm) in pure, buffered, and protein containing aqueous Solutions. We report for the first time oil nanoscale pores formed on ppHex deposits upon exposure to water and Surface blistering of ppHex deposited oil ppAAm in water. We demonstrate that the nature of the Solution influenced the feature formation. These studies are necessary to monitor the changes of the plasma polymer Surfaces applied in cell guidance. The surface chemical and topographical data from single- and double-layer plasma polymer films were compared. We further demonstrate that the differences in surface chemistry and topography that develop during aqueous exposure between the single- and double-layer plasma polymer deposits do not affect the adhesion of cells to the Surface. These novel nanostructured Surfaces may prove useful as membranes or Structured films in biotechnological applications.