Multivalent weak interactions enhance selectivity of interparticle binding.
Multivalent weak interactions enhance selectivity of interparticle binding.
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DOI：
10.1073/pnas.2003968117
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发表时间：
2020-09-15
影响因子：
11.1
通讯作者：
Prins MWJ
中科院分区：
文献类型：
--
作者：
Scheepers MRW;van IJzendoorn LJ;Prins MWJ
胶体粒子的选择性结合是靶向给药领域的一个重要研究课题。大量的理论工作表明，通过使用多价弱相互作用可以获得高选择性。在这里，我们提供了全面的实验证明使用DNA涂层颗粒。通过改变互补碱基的数量来改变配体-受体亲和力，表明较少的互补碱基产生较高的结合选择性。实验数据和相应的数值模型模拟表明，分子密度，分子亲和力，和所得的粒子间结合的密度选择性之间的标度行为。这些结果对于设计新型靶向纳米颗粒药物递送系统具有重要意义。靶向给药关键取决于货物运输胶体颗粒的结合选择性。大量的理论工作表明，两个因素是必要的，以实现高选择性的阈值受体密度：多价和弱相互作用。在这里，我们研究了一个模型系统的DNA包被的粒子与多价和弱相互作用，模仿粒子和细胞之间的配体-受体相互作用。使用光磁簇实验，粒子聚集率作为配体和受体密度的函数进行测量。测量的聚集率表明，结合变得更短的DNA配体-受体对的选择性，证明多价弱相互作用导致增强的选择性粒子间结合。模拟证实了实验结果，并显示了弱多价结合的选择性中的配体-受体解离的作用。
The selectivity of binding of colloidal particles is an important research topic for the field of targeted drug delivery. Extensive theoretical work has shown that high selectivity can be obtained by using multivalent weak interactions. Here we provide comprehensive experimental proof using DNA-coated particles. The ligand–receptor affinity is varied by changing the number of complementary bases, showing that fewer complementary bases yield a higher binding selectivity. The experimental data and corresponding numerical model simulations demonstrate the scaling behavior between molecular density, molecular affinity, and resulting density selectivity of interparticle binding. These results are important for the design of novel systems for targeted nanoparticle drug delivery. Targeted drug delivery critically depends on the binding selectivity of cargo-transporting colloidal particles. Extensive theoretical work has shown that two factors are necessary to achieve high selectivity for a threshold receptor density: multivalency and weak interactions. Here, we study a model system of DNA-coated particles with multivalent and weak interactions that mimics ligand–receptor interactions between particles and cells. Using an optomagnetic cluster experiment, particle aggregation rates are measured as a function of ligand and receptor densities. The measured aggregation rates show that the binding becomes more selective for shorter DNA ligand–receptor pairs, proving that multivalent weak interactions lead to enhanced selectivity in interparticle binding. Simulations confirm the experimental findings and show the role of ligand–receptor dissociation in the selectivity of the weak multivalent binding.
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DOI：
10.1073/pnas.1815912115
发表时间：
2018-11-20
影响因子：
11.1
作者：
Gao A;Shrinivas K;Lepeudry P;Suzuki HI;Sharp PA;Chakraborty AK
通讯作者：
Chakraborty AK
影响因子：
15
作者：
Bhatia, Sumati;Camacho, Luis Cuellar;Haag, Rainer
通讯作者：
Haag, Rainer
影响因子：
4
作者：
Carlson, Coby B.;Mowery, Patricia;Kiessling, Laura L.
通讯作者：
Kiessling, Laura L.
影响因子：
5.6
作者：
WETMUR, JG;DAVIDSON, N
通讯作者：
DAVIDSON, N
影响因子：
4.3
作者：
Joshi, Amit;Vance, David;Kane, Ravi S.
通讯作者：
Kane, Ravi S.