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Conditional DNA-Protein Interactions Confer Stimulus-Sensing Properties to Biohybrid Materials

  作者 Christen, EH; Karlsson, M; Kampf, MM; Schoenmakers, R; Gubeli, RJ; Wischhusen, HM; Friedrich, C; Fussenegger, M; Weber, W  
  选自 期刊  ADVANCED FUNCTIONAL MATERIALS;  卷期  2011年21-15;  页码  2861-2867  
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[摘要]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.

 
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