Abstract:
Cell-cell interactions play an important role in many biological processes, and various methods have been developed for controlling the cell-cell interactions. However, the effective and rapid control of intercellular interactions remains challenging. Herein, we report a novel, rapid, and effective electrochemical strategy without destroying the basic life processes for the dynamic control of intercellular interactions via liposome fusion. In the proposed system, bioorthogonal chemical groups and hydroquinone (HQ)- and aminooxy (AO)-tethered ligands were modified on the surface of living cells on the basis of the liposome fusion, enabling dynamical intercellular assemblies. Upon application of the corresponding oxidative potential, the \"off-state\" HQ could be oxidized to the \"on-state\" quinone (Q), which subsequently reacts with AO-tethered ligands to form stable oxime linkages under physiological conditions. This reaction effectively shortens the distance between cells, promoting the formation of cell clusters. When the corresponding reverse reductive potential is applied, the oxime linkage is cleaved, resulting in the release of the cells. Furthermore, we employed HQ- and AO-tethered ligands to modify mitochondria, inducing mitochondrial aggregation. This noninvasive and label-free strategy allows for the dynamic reversible regulation of intercellular interactions, enhancing our understanding of intercellular communication networks, and has the potential for improving the antitumor therapy efficacy.
摘要:
细胞间的相互作用在许多生物过程中起着重要的作用。并且已经开发了用于控制细胞-细胞相互作用的各种方法。然而,细胞间相互作用的有效和快速控制仍然具有挑战性。在这里,我们报道了一部小说,快速,和有效的电化学策略,而不破坏通过脂质体融合动态控制细胞间相互作用的基本生命过程。在拟议的系统中,在脂质体融合的基础上,在活细胞表面修饰了生物正交化学基团和氢醌(HQ)-和氨基氧基(AO)-连接的配体,实现动态细胞间组装。在施加相应的氧化电势时,“关闭状态”HQ可以被氧化为“打开状态”醌(Q),其随后与AO系链配体反应以在生理条件下形成稳定的肟键。这种反应有效地缩短了细胞之间的距离,促进细胞簇的形成。当施加相应的反向还原电势时,肟键被切断,导致细胞的释放。此外,我们使用HQ和AO系链配体修饰线粒体,诱导线粒体聚集。这种非侵入性和无标记策略允许动态可逆调节细胞间相互作用,增强我们对蜂窝间通信网络的理解,具有提高抗肿瘤治疗疗效的潜力。