Modeling Effects of Surface Properties and Probe Density for Nanoscale Biosensor Design: A Case Study of DNA Hybridization near Surfaces.
Modeling Effects of Surface Properties and Probe Density for Nanoscale Biosensor Design: A Case Study of DNA Hybridization near Surfaces.
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纳米级生物传感器设计的表面特性和探针密度的建模效应：表面附近 DNA 杂交的案例研究。
DOI：
10.1021/acs.jpcb.0c09723
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发表时间：
2021-02-25
期刊：
影响因子：
--
通讯作者：
Chang CA
中科院分区：
文献类型：
--
作者：
Cholko T;Chang CA
电化学生物传感器具有极强的应用前景，同时具有易于制备、小型化和可调谐的特点。通过调整固定探针在传感器表面的排列和性质来优化靶-探针关联，可以设计出高灵敏度和高效率的传感器。在电化学核酸生物传感器中，自组装单分子层(SAM)被广泛地用作可调谐表面，插入DNA或RNA探针来检测目标序列。由于分辨率不高，表面不均匀探针分布的影响很难在实验上研究。高探针密度的区域可能会抑制与目标的杂交，并且影响的大小可能会根据给定表面上的杂交机制而有所不同。另一个基本问题涉及DNA在表面的扩散和杂交，以及它是加速还是阻碍分子识别。我们使用全原子布朗动力学模拟来帮助回答这些问题，方法是模拟单链DNA(SsDNA)靶与单链DNA探针在三种不同探针表面密度下在极性、非极性和阴离子自组装膜上的杂交过程。此外，我们通过在两个不同表面上模拟具有不同探针间距的团簇来模拟三个紧密堆积的探针团簇。我们的结果表明，杂交效率在很大程度上取决于找到一个平衡，允许吸引力将目标DNA导向探针，而不是将其锚定在表面。此外，我们发现当探针间距小于或等于目标DNA长度时，杂交率会严重受阻，这证明需要仔细设计以增强靶探针的关联性和避免空间位阻。我们开发了一个通用的动力学模型来预测杂交时间，发现它对典型的探针密度是准确的。这些发现阐明了纳米级生物传感器的基本特征，这有助于合理的设计工作，并有助于解释不同探针密度下实验杂交率的趋势。
Electrochemical biosensors have extremely robust applications while offering ease of preparation, miniaturization, and tunability. By adjusting the arrangement and properties of immobilized probes on the sensor surface to optimize target–probe association, one can design highly sensitive and efficient sensors. In electrochemical nucleic acid biosensors, a self-assembled monolayer (SAM) is widely used as a tunable surface with inserted DNA or RNA probes to detect target sequences. The effects of inhomogeneous probe distribution across surfaces are difficult to study experimentally due to inadequate resolution. Regions of high probe density may inhibit hybridization with targets, and the magnitude of the effect may vary depending on the hybridization mechanism on a given surface. Another fundamental question concerns diffusion and hybridization of DNA taking place on surfaces and whether it speeds up or hinders molecular recognition. We used all-atom Brownian dynamics simulations to help answer these questions by simulating the hybridization process of single-stranded DNA (ssDNA) targets with a ssDNA probe on polar, nonpolar, and anionic SAMs at three different probe surface densities. Moreover, we simulated three tightly packed probe clusters by modeling clusters with different interprobe spacing on two different surfaces. Our results indicate that hybridization efficiency depends strongly on finding a balance that allows attractive forces to steer target DNA toward probes without anchoring it to the surface. Furthermore, we found that the hybridization rate becomes severely hindered when interprobe spacing is less than or equal to the target DNA length, proving the need for a careful design to both enhance target–probe association and avoid steric hindrance. We developed a general kinetic model to predict hybridization times and found that it works accurately for typical probe densities. These findings elucidate basic features of nanoscale biosensors, which can aid in rational design efforts and help explain trends in experimental hybridization rates at different probe densities.
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影响因子：
17.1
作者：
Josephs, Eric A.;Ye, Tao
通讯作者：
Ye, Tao
影响因子：
5.5
作者：
Bell, Samuel;Terentjev, Eugene M.
通讯作者：
Terentjev, Eugene M.
DOI：
10.1021/acs.jpcb.0c02926
发表时间：
2020-07-09
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Cholko T;Barnum J;Chang CA
通讯作者：
Chang CA
影响因子：
13.3
作者：
Kastantin, Mark;Schwartz, Daniel K.
通讯作者：
Schwartz, Daniel K.
影响因子：
9.5
作者：
Dong, Shibiao;Zhao, Rongtao;Song, HongBin
通讯作者：
Song, HongBin