The engineering of either complete virus cell-binding proteins or derived ligand peptides generates promising nonviral vectors for cell targeting and gene therapy. In this work, we have explored the molecular interaction between a recombinant, integrin-binding foot-and-mouth disease virus RGD peptide displayed on the surface of a carrier protein and its receptors on the cell surface. By increasing the number of viral segments, cell binding to recombinant proteins was significantly improved. This fact resulted in a dramatic growth stimulation of virus-sensitive BHK21 cells but not virus-resistant HeLa cells in protein-coated wells. Surprisingly, growth stimulation was not observed in vitronectin-coated plates, suggesting that integrins other than alpha (v)beta (3) could be involved in binding of the recombinant peptide, maybe as coreceptors. On the other hand, both free and cell-linked integrins did not modify the enzymatic activity of BOB-based enzymatic sensors that contrarily, were activated by the induced fit of anti-BOB antibodies. Those findings are discussed in the context of a proper mimicry of the unusually complex architecture of this cell-binding site as engineered in multifunctional proteins.