Nanomechanics of drug-target interactions and antibacterial resistance detection.
Nanomechanics of drug-target interactions and antibacterial resistance detection.
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DOI：
10.3791/50719
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发表时间：
2013-10-25
期刊：
影响因子：
--
通讯作者：
McKendry RA
中科院分区：
文献类型：
--
作者：
Ndieyira JW;Watari M;McKendry RA
悬臂梁传感器，它作为一个传感器之间的反应模型细菌细胞壁基质固定在其表面和抗生素药物在溶液中，已显示出相当大的潜力，在生化传感应用与前所未有的灵敏度和特异性1 -5。药物-靶标相互作用产生表面应力，导致悬臂弯曲，并且当其被激光照射时可以光学地分析信号。以纳米级精度测量的表面应力的变化允许真实的时间跟踪模型细菌细胞壁靶的生物力学的破坏。尽管提供了相当大的优势，多个悬臂梁传感器阵列从来没有被应用于定量药物靶结合相互作用。在这里，我们报告了使用硅多悬臂阵列涂有烷乙醇自组装单层模仿细菌细胞壁基质定量研究抗生素结合的相互作用。为了了解万古霉素对细菌细胞壁结构力学的影响1，6，7。我们开发了一个新模型1，提出悬臂梁弯曲可以由两个独立因素描述; i）即化学因子，其由经典的朗缪尔吸附等温线给出，从中我们计算热力学平衡解离常数（Kd），和ii）几何因子，基本上是衡量细菌肽受体如何分布在悬臂表面上。肽受体（p）的表面分布用于研究几何形状和配体负载的依赖性。它示出的阈值的p ~10%是至关重要的传感应用。低于该值时没有可检测到的弯曲信号，而高于该值时，弯曲信号几乎线性增加，揭示了应力是局部化学结合因子和由反应区域的机械连接性组合的几何因子的产物，并为设计强大的药剂以对抗超级细菌感染提供了新的范例。
The cantilever sensor, which acts as a transducer of reactions between model bacterial cell wall matrix immobilized on its surface and antibiotic drugs in solution, has shown considerable potential in biochemical sensing applications with unprecedented sensitivity and specificity1-5. The drug-target interactions generate surface stress, causing the cantilever to bend, and the signal can be analyzed optically when it is illuminated by a laser. The change in surface stress measured with nano-scale precision allows disruptions of the biomechanics of model bacterial cell wall targets to be tracked in real time. Despite offering considerable advantages, multiple cantilever sensor arrays have never been applied in quantifying drug-target binding interactions. Here, we report on the use of silicon multiple cantilever arrays coated with alkanethiol self-assembled monolayers mimicking bacterial cell wall matrix to quantitatively study antibiotic binding interactions. To understand the impact of vancomycin on the mechanics of bacterial cell wall structures1,6,7. We developed a new model1 which proposes that cantilever bending can be described by two independent factors; i) namely a chemical factor, which is given by a classical Langmuir adsorption isotherm, from which we calculate the thermodynamic equilibrium dissociation constant (Kd) and ii) a geometrical factor, essentially a measure of how bacterial peptide receptors are distributed on the cantilever surface. The surface distribution of peptide receptors (p) is used to investigate the dependence of geometry and ligand loading. It is shown that a threshold value of p ~10% is critical to sensing applications. Below which there is no detectable bending signal while above this value, the bending signal increases almost linearly, revealing that stress is a product of a local chemical binding factor and a geometrical factor combined by the mechanical connectivity of reacted regions and provides a new paradigm for design of powerful agents to combat superbug infections.
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影响因子：
48
作者：
Godin, Michel;Delgado, Francisco Feijo;Son, Sungmin;Grover, William H.;Bryan, Andrea K.;Tzur, Amit;Jorgensen, Paul;Payer, Kris;Grossman, Alan D.;Kirschner, Marc W.;Manalis, Scott R.
通讯作者：
Manalis, Scott R.
影响因子：
64.5
作者：
Kohanski MA;Dwyer DJ;Wierzbowski J;Cottarel G;Collins JJ
通讯作者：
Collins JJ
影响因子：
56.9
作者：
PRIME, KL;WHITESIDES, GM
通讯作者：
WHITESIDES, GM
影响因子：
56.9
作者：
Fritz, J;Baller, MK;Gimzewski, JK
通讯作者：
Gimzewski, JK
影响因子：
2.9
作者：
BUGG, TDH;WRIGHT, GD;WALSH, CT
通讯作者：
WALSH, CT