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This paper describes a molecular strategy to restore adhesion of cells to surfaces that otherwise do not present ligands that can mediate adhesion. The approach is based on a carbonic anhydrase fusion protein that binds benzenesulfonamides and that also includes the RGD peptide motif that can bind to cell-surface integrin adhesion receptors. In this way, the fusion protein can bind to a monolayer that presents the benzenesulfonamide ligand, thereby positioning the RGD peptide at the surface, where it can mediate the adhesion and spreading of cells. This strategy may provide a general method for promoting the adhesion of cells to non-natural surfaces or to defective biological matrices.

Nephronectin is an extracellular matrix protein that interacts with the α8β1 integrin receptor and plays a role in tissue and organ development, though the motifs that mediate adhesion to the receptor remain unclear. This paper describes the use of self-assembled monolayers to study the adhesion of α8β1-presenting cells to the RGD and DLFEIFEIER ligands in nephronectin and found that both ligands can independently mediate cell adhesion through nonoverlapping binding sites on the integrin. Peptide truncation experiments showed FEI to be the minimal binding sequence within the DLFEIFEIER sequence, and adhesion experiments with peptides that include both the RGD and FEI sequences demonstrate that the two peptides bind synergistically to the receptor. Finally, a peptide array was used to establish a strict requirement for the glutamate residue of FEI and tolerance of other aromatic and hydrophobic residues in the first and third positions, respectively. This work provides an enhanced understanding of the binding of nephronectin with α8β1 and identifies a peptide ligand that can be used for targeting the α8β1 integrin.