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Genetically targeted chemical assembly of functional materials in living cells, tissues, and animals
Science ( IF 44.7 ) Pub Date : 2020-03-19 , DOI: 10.1126/science.aay4866
Jia Liu 1 , Yoon Seok Kim 2 , Claire E Richardson 3 , Ariane Tom 2 , Charu Ramakrishnan 2 , Fikri Birey 4 , Toru Katsumata 1 , Shucheng Chen 1 , Cheng Wang 5 , Xiao Wang 2 , Lydia-Marie Joubert 6 , Yuanwen Jiang 1 , Huiliang Wang 2 , Lief E Fenno 2, 4 , Jeffrey B-H Tok 1 , Sergiu P Pașca 4 , Kang Shen 3, 7 , Zhenan Bao 1 , Karl Deisseroth 2, 4, 7
Affiliation  

From genetics to material to behavior Introducing new genes into an organism can endow new biochemical functions or change the patterns of existing functions, but extending these manipulations to structure at the tissue level is challenging. Combining genetic engineering and polymer chemistry, Liu et al. directly leveraged complex cellular architectures of living organisms to synthesize, fabricate, and assemble bioelectronic materials (see the Perspective by Otto and Schmidt). An engineered enzyme expressed in genetically targeted neurons synthesized conductive polymers in tissues of freely moving animals. These polymers enabled modulation of membrane properties in specific neuron populations and manipulation of behavior in living animals. Science, this issue p. 1372; see also p. 1303 Engineered enzymes employed in neurons enable synthesis of electroactive polymers for behavior remodeling in living animals. The structural and functional complexity of multicellular biological systems, such as the brain, are beyond the reach of human design or assembly capabilities. Cells in living organisms may be recruited to construct synthetic materials or structures if treated as anatomically defined compartments for specific chemistry, harnessing biology for the assembly of complex functional structures. By integrating engineered-enzyme targeting and polymer chemistry, we genetically instructed specific living neurons to guide chemical synthesis of electrically functional (conductive or insulating) polymers at the plasma membrane. Electrophysiological and behavioral analyses confirmed that rationally designed, genetically targeted assembly of functional polymers not only preserved neuronal viability but also achieved remodeling of membrane properties and modulated cell type–specific behaviors in freely moving animals. This approach may enable the creation of diverse, complex, and functional structures and materials within living systems.

中文翻译:

活细胞、组织和动物中功能材料的基因靶向化学组装

从遗传到材料再到行为将新基因引入生物体可以赋予新的生化功能或改变现有功能的模式,但将这些操作扩展到组织水平的结构具有挑战性。结合基因工程和高分子化学,刘等。直接利用生物体的复杂细胞结构来合成、制造和组装生物电子材料(参见 Otto 和 Schmidt 的观点)。在基因靶向神经元中表达的工程酶在自由移动的动物组织中合成了导电聚合物。这些聚合物能够调节特定神经元群体的膜特性并操纵活体动物的行为。科学,这个问题 p。第1372章 另见第 1303 神经元中使用的工程酶能够合成电活性聚合物,以重塑活体动物的行为。多细胞生物系统(如大脑)的结构和功能复杂性超出了人类设计或组装能力的范围。如果将生物体中的细胞视为特定化学的解剖学定义的隔室,则可以招募活生物体中的细胞来构建合成材料或结构,利用生物学来组装复杂的功能结构。通过整合工程酶靶向和聚合物化学,我们对特定的活神经元进行遗传指导,以指导质膜上电功能(导电或绝缘)聚合物的化学合成。电生理和行为分析证实,合理设计,功能聚合物的基因靶向组装不仅保留了神经元的活力,而且还实现了膜特性的重塑,并在自由移动的动物中实现了细胞类型特异性行为的调节。这种方法可以在生命系统中创造多样化、复杂和功能性的结构和材料。
更新日期:2020-03-19
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