In situ genetically targeted chemical assembly of polymers on living neuronal membranes
In situ genetically targeted chemical assembly of polymers on living neuronal membranes
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DOI：
10.1101/2022.12.27.521974
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发表时间：
2022-12
期刊：
影响因子：
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通讯作者：
Anqi Zhang;K. Y. Loh;Chandan S. Kadur;Lukas Michalek;Jiayi Dou;C. Ramakrishnan;Zhenan Bao;K. Deisseroth
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文献类型：
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作者：
Anqi Zhang;K. Y. Loh;Chandan S. Kadur;Lukas Michalek;Jiayi Dou;C. Ramakrishnan;Zhenan Bao;K. Deisseroth
多细胞生物系统，尤其是活神经网络，表现出高度复杂的物理组织特性，这给构建细胞特异性和生物相容性界面带来了挑战。我们开发了一种新的方法，通过基因编程细胞来化学组装人工结构，从而原位修改神经元的电学特性，从而开辟了与活体动物的神经回路进行微创细胞特异性界面的可能性。然而，这种方法的效率和生物相容性受到构建材料的有限膜靶向性的挑战。在这里，我们报告了一种具有显著改进的分子结构特性的方法，该方法表达了针对初级神经元质膜的高度定位的酶，细胞内保留最小。通过这种方法原位合成的聚合物在目标细胞膜上形成密集的簇，聚合后神经元仍能存活。这个平台可以很容易地扩展到将广泛的材料结合到复杂组织内特定细胞的表面膜上，使用化学可以进一步实现与活生物系统的下一代界面。
Multicellular biological systems, most notably living neural networks, exhibit highly complex physical organization properties that pose challenges for building cell-specific and biocompatible interfaces. We developed a novel approach to genetically program cells to chemically assemble artificial structures that modify the electrical properties of neurons in situ, opening up the possibility of minimally-invasive cell-specific interfaces with neural circuits in living animals. However, the efficiency and biocompatibility of this approach were challenged by limited membrane targeting of the constructed material. Here, we report a method with significantly improved molecular construct properties, which expresses highly localized enzymes targeted to the plasma membrane of primary neurons with minimal intracellular retention. Polymers synthesized in situ by this approach form dense clusters on the targeted cell membrane, and neurons remain viable after polymerization. This platform can be readily extended to incorporate a broad range of materials onto the surface membranes of specific cells within complex tissues, using chemistry that may further enable the next generation of interfaces with living biological systems.