Ligand-receptor interactions in tethered polymer layers
Ligand-receptor interactions in tethered polymer layers
复制标题
DOI：
10.1021/la051685p
复制
发表时间：
2005-11-22
期刊：
影响因子：
3.9
通讯作者：
Szleifer, I
中科院分区：
文献类型：
--
作者：
Longo, G;Szleifer, I
用分子理论研究了小分子蛋白质与连接在平面上的聚合物游离端的配体的结合。研究了改变配体-受体对的内禀结合平衡常数、聚合物表面覆盖度、聚合物相对分子质量和蛋白质大小的影响。还将结果与配体直接连接到表面而不使用聚合物作为间隔基的情况进行了比较。我们发现，在结合常数的生物学范围内，聚合物间隔物的存在增强了蛋白质的吸附。总有一个最佳的表面覆盖率，其中配体-受体结合是最大的。这一最大值随着结合能和/或聚合物分子量的增加而增加。最大值的存在是由于聚合物结合蛋白的能力，通过在空间中分散配体来形成厚层，以优化结合并将侧向斥力降至最低。对于很小的配体表面覆盖率，结合受体的比例是统一的。结合配体-受体对的比例随表面覆盖率的急剧下降取决于聚合物间隔链的长度。我们发现，蛋白质的结合力随着蛋白质大小的增加而减少。通过选择合适的接枝层条件，可以控制结合蛋白的取向。在高表面覆盖率时，结合蛋白主要垂直于表面，而在低表面覆盖率时，有更随机的取向分布。为了避免非特异性吸附在表面，我们研究了自由端连接有配体的相对高分子量聚合物和没有配体的低分子量聚合物的混合物覆盖表面的情况。这些体系在蛋白质结合方面表现出最大值，与仅存在长聚合物配体时的大小相同。此外，当聚合物混合层的总表面覆盖率足够高时，蛋白质在表面上的非特异性吸附被抑制。讨论了利用所提出的理论结果来设计具有特定蛋白质结合能力和最佳无污染能力的表面修饰剂。
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.