Conditional DNA-Protein Interactions Confer Stimulus-Sensing Properties to Biohybrid Materials
Conditional DNA-Protein Interactions Confer Stimulus-Sensing Properties to Biohybrid Materials
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DOI：
10.1002/adfm.201100731
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发表时间：
2011-08-09
影响因子：
19
通讯作者：
Weber, Wilfried
中科院分区：
文献类型：
--
作者：
Christen, Erik H.;Karlsson, Maria;Weber, Wilfried
专门响应环境刺激的交互式材料在生物医学，分析或微系统工程中作为能量自主传感器和执行器具有很高的前景。然而，到目前为止，对给定小分子特异性响应的材料的实施受到缺乏通用刺激传感器的阻碍。在这项研究中，一个新的和可能的一般策略，合成生物杂交材料与所需的刺激特异性。该策略基于变构调节的DNA结合蛋白，这是一种保守的蛋白质家族，在原核生物中进化为感知和响应最多样化的分子，以使细菌能够在不断变化的环境中生存。新的水凝胶设计概念与单链TetR的例子证明，一种蛋白质，结合tetO DNA基序和解离的抗生素四环素的存在下。因此，线性聚丙烯酰胺通过TetR/tetO相互作用交联成生物杂交材料，该生物杂交材料随后可以以剂量依赖性方式被四环素溶解。这种药物诱导的溶解以四环素依赖性方式用于细胞因子白细胞介素4的可调节释放。在这项研究中开发的设计概念可能作为一个蓝图的生物杂交材料的合成响应药物，代谢产物或毒素取代TetR/tetO与另一种蛋白质/DNA对显示所需的刺激特异性。
Interactive materials that specifically respond to environmental stimuli hold high promise as energy-autonomous sensors and actuators in biomedicine, analytics or microsystems engineering. However, the implementation of materials specifically responsive to a given small molecule has so far been hampered by a lack of generically applicable stimulus sensors. In this study, a novel and likely general strategy for the synthesis of biohybrid materials with desired stimulus specificity is established. The strategy is based on allosterically regulated DNA-binding proteins, a conserved protein family that has evolved in prokaryotes to sense and respond to most diverse molecules in order to enable bacterial survival in a changing environment. The novel hydrogel design concept is demonstrated with the example of single-chain TetR, a protein that binds the tetO DNA motif and dissociates thereof in the presence of the antibiotic tetracycline. Therefore, linear polyacrylamide is crosslinked via the TetR/tetO interaction to a biohybrid material that can subsequently be dissolved by tetracycline in a dose-dependent manner. This drug-induced dissolution is applied for the adjustable release of the cytokine interleukin 4 in a tetracycline-dependent manner. The design concept developed in this study might serve as a blueprint for the synthesis of biohybrid materials responsive to drugs, metabolites or toxins by replacing TetR/tetO with another protein/DNA pair showing the desired stimulus specificity.