Optimization of functionalized polymer layers for specific targeting of mobile receptors on cell surfaces.
Optimization of functionalized polymer layers for specific targeting of mobile receptors on cell surfaces.
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DOI：
10.1021/la801935h
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发表时间：
2008-11-18
期刊：
影响因子：
--
通讯作者：
Dormidontova EE
中科院分区：
文献类型：
--
作者：
Hagy MC;Wang S;Dormidontova EE
通过Monte Carlo模拟研究了由靶向基团官能化的平面聚合物层与含有不同密度的移动的受体的平面细胞表面之间的可逆结合。使用接受比方法的距离依赖的配置文件的平均数的配体结合到受体，总自由能的聚合物层细胞表面相互作用和相互作用力。聚合物层的四个主要设计参数被认为是：官能化程度，链聚合度，接枝的聚合物密度和靶向基团-受体相互作用的结合能。我们发现，增加的功能化程度或在配体-受体结合的绝对能量的结果在更大数量的配体结合到受体，更低的自由能和更强的吸引力。发现由较短链组成的聚合物层表现出更深和更窄的自由能分布和更大的吸引力，而较长的系链可以在更大和更宽的分离距离范围内与细胞表面相互作用，与实验观察一致。我们的模拟结果表明，从蘑菇刷政权的聚合物接枝密度的增加增强了配体的可用性，并在一个更强的吸引力的结果，增加了最大结合距离，但表现出较浅的自由能最小值，由于较小的公差压缩的聚合物层与高接枝密度。我们使用了两个措施的聚合物层的细胞表面的结合亲和力：自由能最小值，有关的平衡结合常数和结合配体的分数。我们发现，具有较小的链长和接枝密度，较大的官能化程度和较大的绝对结合能的聚合物层表现出较大的平衡结合常数的细胞表面和结合配体的平均数较大，除了高结合能时，达到最大水平的结合独立的聚合物长度和接枝密度。我们表明，高结合特异性可以通过具有中间配体-受体结合能或中间配体数量的聚合物层来实现，因为较大的结合能或配体数量确保了高结合亲和力但缺乏特异性，而较小的结合能或配体数量提供了不足的亲和力。我们发现，当考虑到对具有高受体密度和高结合特异性的细胞的高结合亲和力时，具有不同性质的聚合物层的结果遵循类似的模式。因此，可以通过使用几种不同的策略来实现聚合物层的优化设计，并进行了讨论。
The reversible binding between a planar polymer layer functionalized by targeting groups and a planar cell surface containing different densities of mobile receptors has been studied by Monte Carlo simulations. Using the acceptance-ratio method the distance-dependent profiles for the average number of ligands bound to receptors, the total free energy for the polymer layer-cell surface interaction and the interaction force were obtained. Four main design parameters for the polymer layer were considered: the degree of functionalization, chain degree of polymerization, polymer density of grafting and the binding energy for the targeting group-receptor interaction. We found that an increase in the degree of functionalization or in the absolute energy of ligand-receptor binding results in a larger number of ligands bound to the receptors, lower free energy and stronger attractive force. Polymer layers composed of shorter chains were found to exhibit a deeper and narrower free energy profile and a larger attractive force, while longer tethers can interact with the cell surface at a larger and broader range of separation distances, in agreement with experimental observations. Our simulation results show that the increase in polymer grafting density from the mushroom to brush regime enhances the ligand availability and results in a stronger attractive force, increases the maximum binding distance, but exhibits a shallower free energy minimum due to the smaller tolerance to compression for polymer layers with high grafting density. We used two measures of the polymer layer binding affinity to the cell surface: the free energy minimum, related to the equilibrium binding constant and the fraction of bound ligands. We found that the polymer layers with a smaller chain length and grafting density, larger degree of functionalization and larger absolute binding energy exhibit both a larger equilibrium binding constant to the cell surface and a larger average number of bound ligands, except for high binding energies when the maximum level of binding is reached independently of polymer length and grafting density. We showed that high binding specificity can be achieved by the polymer layers with intermediate ligand-receptor binding energies or an intermediate number of ligands, as a larger binding energy or number of ligands ensures a high binding affinity but lacks specificity while a smaller binding energy or number of ligands provides inadequate affinity. We found that the results for polymer layers with different properties follow a similar pattern when both high binding affinity to cells with high receptor density and high binding specificity are considered. As a result, the optimal design of the polymer layers can be achieved by using several different strategies, which are discussed.
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影响因子：
4.1
作者：
BENNETT, CH
通讯作者：
BENNETT, CH
影响因子：
3.4
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