Programming Cell-Cell Communications with Engineered Cell Origami Clusters
Programming Cell-Cell Communications with Engineered Cell Origami Clusters
复制标题
使用工程细胞折纸簇对细胞间通信进行编程
DOI：
10.1021/jacs.0c01580
复制
发表时间：
2020-05-13
影响因子：
15
通讯作者：
Fan, Chunhai
中科院分区：
文献类型：
--
作者：
Ge, Zhilei;Liu, Jiangbo;Fan, Chunhai
以簇形式存在的细胞通常表现出与单分散形式不同的生理功能，与组织和器官发育、免疫反应和癌症转移密切相关。然而，构建人工细胞簇作为探测和操纵细胞间通讯的体外模型的能力仍然有限。在这里，我们设计了基于 DNA 折纸纳米结构 (DON) 的仿生膜通道，以组织具有受控几何配置和细胞间通信的细胞折纸簇 (COC)。我们证明，具有不同配置的同型和异型 COC 的可编程图案可以导致三种不同类型的细胞间通讯：间隙连接、隧道纳米管和免疫/肿瘤细胞相互作用。特别是，按照规定的比例和几何形状组织 T 细胞和癌细胞可以对体外免疫反应进行编程，为理解和设计癌症免疫疗法提供了一条新途径。
Cells existing in the form of clusters often exhibit distinct physiological functions from their monodispersed forms, which have a close association with tissue and organ development, immunoresponses, and cancer metastasis. Nevertheless, the ability to construct artificial cell clusters as in vitro models for probing and manipulating intercellular communications remains limited. Here we design DNA origami nanostructure (DON)-based biomimetic membrane channels to organize cell origami clusters (COCs) with controlled geometric configuration and cell-cell communications. We demonstrate that programmable patterning of homotypic and heterotypic COCs with different configurations can result in three distinct types of intercellular communications: gap junctions, tunneling nanotubes, and immune/tumor cell interactions. In particular, the organization of T cells and cancer cells with a prescribed ratio and geometry can program in vitro immunoresponses, providing a new route to understanding and engineering cancer immunotherapy.