Nanoscale Adhesion Ligand Organization Regulates Osteoblast Proliferation and Differentiation

It was hypothesized that nanoscale adhesion ligand spacing regulates cell adhesion, proliferation, and differentiation, and that this control can be decoupled from the overall ligand density. Alginate was chemically modified with a peptide containing the cell adhesion sequence arginine-glycine-aspartic acid (RGD), and the nanoscale spacing of RGD ligands in alginate gels was varied. A decrease in the RGD island spacing from 78 to 36 nm upregulated the proliferation rates of MC3T3-E1 cells from 0.59 ± 0.08 to 0.73 ± 0.03 day^-1 and resulted in 4-fold increase of the osteocalcin secretion rate. This finding was independent of the bulk ligand density of gels. These results indicate that nanoscale ligand organization may provide an important variable to regulate cell functions in many biomedical applications, including tissue engineering.