Facilitating tissue regeneration or replacement requires development of synthetic surfaces that promote cell adhesion, migration, and proliferation. Two successful approaches have been to incorporate minimal cell adhesion recognition sequences at the biomaterial surface and to integrate the entire adhesion molecule into a compatible synthetic matrix. While adhesion assays using immortalized cell lines are important in evaluating synthetic materials, cell type and source play a significant role in the ability of such models to mimic real tissues. Models that utilize multiple cell types or primary cells are more representative of native tissues than models that use single cell types or primary cells. In this study we investigated primary respiratory epithelial cell (REC) adhesion to modified fluoropolymers incorporating simple functional groups and minimal peptide recognition sequences, and we evaluated the potential of hybrid biopolymer materials to support adhesion and proliferation. X-ray photoelectron spectroscopy (XPS) was used to verify substrate surface composition. Significant differences were found in the adhesion characteristics of primary REC and in the A549 lung carcinoma cell line. Model systems composed of multiple cell types and/or primary cells necessarily represent increased levels of complexity for an investigation of cellular responses to synthetic surfaces. When evaluating biomaterials, adhesion studies using immortalized cell lines cannot necessarily be extrapolated to normal cell behavior.