Ligand-receptor interactions in tethered polymer layers.
The binding of small proteins to ligands that are attached to the free ends of polymers tethered to a planar surface is studied using a molecular theory. The effects of changing the intrinsic binding equilibrium constant of the ligand-receptor pair, the polymer surface coverage, the polymer molecular weight, and the protein size are studied. The results are also compared with the case where ligands are directly attached to the surface without a polymer acting as a spacer. We found that within the biological range of binding constants the protein adsorption is enhanced by the presence of the polymer spacers. There is always an optimal surface coverage for which ligand-receptor binding is a maximum. This maximum increases as the binding energy and/or the polymer molecular weight increase. The presence of the maximum is due to the ability of the polymer-bound proteins to form a thick layer by dispersing the ligands in space to optimize binding and minimize lateral repulsions. The fraction of bound receptors is unity for a very small surface coverage of ligands. The very sharp decrease in the fraction of bound ligand-receptor pairs with surface coverage depends on the polymer spacer chain length. We found that the binding of proteins is reduced as the size of the protein increases. The orientation of the bound proteins can be manipulated by proper choice of the grafted layer conditions. At high polymer surface coverage the bound proteins are predominantly perpendicular to the surface, while at low surface coverage there is a more random distribution of orientations. To avoid nonspecific adsorption on the surface, we studied the case where the surface is covered by a mixture of a relatively high molecular weight polymer with a ligand attached to its free end and a low molecular weight polymer without ligand. These systems present a maximum in the binding of proteins, which is of the same magnitude as when only the long polymer-ligand is present. Moreover, when the total surface coverage in the mixed layers of polymers is high enough, nonspecific adsorption of the proteins on the surface is suppressed. The use of the presented theoretical results for the design of surface modifiers with tailored abilities for specific binding of proteins and optimal nonfouling capabilities is discussed.
Longo
Gabriel
G
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
Szleifer
I
I
D000327:Adsorption; D008024:Ligands; D011108:Polymers / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D013499:Surface Properties
D008024:Ligands; D011108:Polymers; D011506:Proteins