Ionic elastin-like polymer (ELP) conjugates are a new class of biocompatible, self-assembling biomaterials. These polymers, consisting of the repeat unit (GVGVP)n, are derived from the primary sequence of mammalian elastin and produced in E. coli. These biopolymers exhibit an inverse transition temperature that renders them extremely useful for applications in cell-sheet engineering. Cationic and anionic conjugates were synthesized by the chemical coupling of ELP to poly-ethyleneimine (PEI) and poly-acrylic acid (PAA) respectively. The self-assembly of PEI-ELP and PAA-ELP into multilayers is a simple, versatile technique to generate bioactive surfaces with the ability to modulate cell-matrix interactions. Our studies are focused on cellular response to self-assembled multilayers of ionic (GVGVP)40. We report significant differences in projected cell areas, cell proliferation, cell adhesion, and cytoskeletal organization with the number of layers in each assembly. Angle-dependent XPS studies were utilized to quantify the chemical composition at the surface (~ 15Angstrom below the surface) and sub-surface (~ 80 Angstrom below the surface). These studies provided additional insight into the growth of the multilayer assembly as well as the chemical environment that the cells sense. We are also currently studying the use of ELP multilayers to generate three-dimensional hepatic constructs. Finally, the ability to tune cell-ELP matrix interactions will allow for control over heterotypic cellular interactions in stratified three-dimensional tissue engineered constructs.