Design and synthesis of a potent peptide containing both specific and non-specific cell-adhesion motifs

This article reports a potent chemical to promote cell adhesion on a substrate by combination of both moieties for specific and non-specific adhesion. The cyclic (-RGDfK-) (R: arginine, G: glycine, D: aspartic acid, f: d-phenylalanine, K: lysine) is employed to trigger specific cell adhesion, and a linear tripeptide KKK is introduced to enhance early non-specific cell adhesion. A series of cyclic and linear peptides with different charges were synthesized and then functionalized with thiol end-group. All the peptides were immobilized on gold layers, which were later passivated by bovine serum albumin. The coverage of NIH/3T3 fibroblast cells on the substrate modified by the linker containing both cyclic (-RGDfK-) and linear KKK is, surprisingly, significantly better than the summation using one of them, which reveals the strong cooperativity of specific and non-specific cell adhesions. The resultant cell adhesion on the substrates modified by appropriate linkers was much better than on tissue-culture plates. The cooperativity principle and the design strategy of the combined linker might be helpful for fundamental research of cell-material or cell-extracellular matrix interactions, and for modification of new biomaterials in regenerative medicine and targeted drug delivery.