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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.

Fibrinogen (Fbg) mediates platelet aggregation by binding the alphaIIbbeta3 integrin receptor, but the interaction of the receptor with peptide motifs of Fbg remains unresolved. This paper describes the use of self-assembled monolayers (SAMs) to study the adhesion of alphaIIbbeta3-transfected CHO cells to the GRGDS and HHLGGAKQAGDV motifs within Fbg. Cells adhered to and spread on monolayers presenting either peptide. Cell adhesion could be inhibited by either soluble peptide, demonstrating that the peptides bind competitively to the integrin. A peptide array was used to show that AGD was the minimal binding sequence in HHLGGAKQAGDV and that the receptor recognizes ligands of the form GXGDSC, where X is a hydrophobic or basic residue. This work revises our understanding of the alphaIIbbeta3 specificity and also suggests a new class of antithrombotic agents.