The protein binding capability of biomaterial surfaces can significantly affect subsequent biological responses, and appropriate ligand presentation is often required to guarantee the best functions. Herein, a new facile method for regulating this capability by varying the localized and average ligand density is presented. Binding between lysine and plasminogen relevant to a fibrinolysis system was chosen as a model. We integrated different lysine-modified β-cyclodextrin (β-CD) derivatives onto bioinert copolymer brushes via host-guest interactions. The localized and average lysine density can be conveniently modulated by changing the lysine valency on β-CD scaffolds and by diluting lysine-persubstituted β-CD with pure β-CD, respectively. Both the plasminogen adsorption and the plasminogen binding affinity were enhanced by lysine-persubstituted β-CD compared with those of lysine-monosubstituted β-CD, which is possibly due to the higher localized lysine density and the multivalent binding of plasminogen on lysine-persubstituted β-CD surfaces. With a change in the ratio of lysine-persubstituted β-CD to β-CD, the average lysine density can be tuned, leading to the linear regulation of the adsorption of plasminogen on surfaces.
