▲ 作者:Jia Liu、Yoon Seok Kim、Claire E. Richardson,et al.
▲ 連結:
https://science.sciencemag.org/content/367/6484/1372
▲ 摘要:
與光遺傳學(即用雷射脈衝調節轉基因神經元的行為)類似,新興的生物電子醫學力圖用電刺激產生細胞或器官特異性效應。
許多細胞和組織(特別是神經元)會對電場作出反應,而電刺激已被證明會影響多種細胞活動。然而,目前的此類方法會常會影響大量、多樣的細胞群或脫靶組織成分,從而產生不良的副作用。
迄今為止,還沒有方法能夠整合具有細胞類型特異性的電活性聚合物,並因而能夠更加有針對性地利用電場和刺激。
這裡,研究人員推出了首個基因靶向的化學組裝法。他們設計了一種酶,它在表達後可指示以基因為標靶的神經元合成電活性聚合物,並將其組裝到其質膜上,從而有效地改變特定細胞群的電屬性。
這種具針對性的方法可用於對體內神經元特性,以及可自由移動的秀麗隱杆線蟲的特定行為,進行生物電子操縱而不會損害這些細胞的天然功能。這種新方法或能在活體系統中創建各種複雜及功能性的合成結構與物質。
▲ Abstract
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 ofcomplex 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.