The Cancer Hospital of the University of Chinese Academy of Sciences, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
J Am Chem Soc. 2021 Mar 31;143(12):4585-4592. doi: 10.1021/jacs.0c11245. Epub 2021 Mar 18.
Cells sense and respond to the external environment, mainly through proteins presented on the membrane where their expression and conformation are dynamically regulated via intracellular programs. Here, we engineer a cell-surface nanoarchitecture that realizes molecular-recognition-initiated DNA assembly to mimic the dynamic behavior of membrane proteins, enabling the manipulation of cellular interaction in response to environmental changes. Our results show that this membrane-anchored DNA nanoarchitecture can be specifically activated by cell-responsive signals to external stimulation. Accordingly, multiple functional modules can be assembled onto the membrane to equip the cell with cell-type-specific binding and killing. This system is expected to offer a new paradigm for engineering therapeutic cells with customized sensing/response pathways.
细胞通过细胞膜上表达的蛋白质感知和响应外部环境，这些蛋白质的表达和构象通过细胞内程序进行动态调节。在这里，我们设计了一种细胞表面纳结构，实现了分子识别引发的 DNA 组装，以模拟膜蛋白的动态行为，从而能够根据环境变化操纵细胞间的相互作用。我们的结果表明，这种膜锚定的 DNA 纳结构可以被细胞响应信号特异性地激活，以对外界刺激作出反应。因此，可以将多个功能模块组装到膜上，使细胞具有特定于细胞类型的结合和杀伤能力。该系统有望为工程化具有定制传感/响应途径的治疗细胞提供新的范例。
