Abstract:
Oligomerization of cellular membrane receptors plays crucial roles in activating intracellular downstream signaling cascades for controlling cellular behaviors in physiological and pathological processes. However, the reversible and controllable regulation of receptors in a user-defined manner remains challenging. Herein, we developed a versatile DNA nanorobot (nR) with installed aptamers and hairpin structures to reversibly and controllably regulate cell migration. This was achieved by dimerization and de-dimerization of mesenchymal-epithelial transition (Met) receptors through DNA strand displacement reactions. The functionalized DNA nR not only plays similar roles as hepatocyte growth factor (HGF) in inducing cell migration but also allows a downgrade to the original state of cell migration. The advanced DNA nanomachines can be flexibly designed to target other receptors for manipulating cellular behaviors and thus represent a powerful tool for the future of biological and medical engineering.
摘要:
细胞膜受体的寡聚化在激活细胞内下游信号级联以控制生理和病理过程中的细胞行为中起着至关重要的作用。然而,以用户定义的方式对受体的可逆和可控调节仍然具有挑战性。在这里,我们开发了一种多功能的DNA纳米机器人(nR),安装了适体和发夹结构,以可逆和可控地调节细胞迁移。这是通过经由DNA链置换反应的间充质-上皮转化(Met)受体的二聚化和去二聚化来实现的。功能化的DNAnR不仅在诱导细胞迁移中发挥与肝细胞生长因子(HGF)相似的作用,而且还可以降低到细胞迁移的原始状态。先进的DNA纳米机器可以灵活地设计为靶向其他受体来操纵细胞行为,因此代表了生物和医学工程未来的强大工具。