Department of Chemistry, Fudan University, Shanghai, China.
Nat Chem. 2024 Sep;16(9):1418-1426. doi: 10.1038/s41557-024-01519-8. Epub 2024 Apr 24.
Natural gap junctions are a type of channel protein responsible for intercellular signalling and mass communication. However, the scope of applications for these proteins is limited as they cannot be prepared at a large scale and are unable to spontaneously insert into cell membranes in vitro. The construction of artificial gap junctions may provide an alternative strategy for preparing analogues of the natural proteins and bottom-up building blocks necessary for the synthesis of artificial cells. Here we show the construction of artificial gap junction channels from unimolecular tubular molecules consisting of alternately arranged positively and negatively charged pillar[5]arene motifs. These molecules feature a hydrophobic-hydrophilic-hydrophobic triblock structure that allows them to efficiently insert into two adjacent plasma membranes and stretch across the gap between the two membranes to form gap junctions. Similar to natural gap junction channels, the synthetic channels could mediate intercellular signal coupling and reactive oxygen species transmission, leading to cellular activity.
天然间隙连接是一种负责细胞间信号传递和物质交流的通道蛋白。然而，由于这些蛋白质不能大规模制备，并且不能在体外自发插入细胞膜，因此它们的应用范围有限。人工间隙连接的构建可能为制备天然蛋白质的类似物以及合成人工细胞所需的自下而上的构建块提供一种替代策略。在这里，我们展示了由交替排列的带正电荷和带负电荷的柱[5]芳烃基元组成的单分子管状分子构建人工间隙连接通道。这些分子具有疏水-亲水-疏水三嵌段结构，允许它们有效地插入两个相邻的质膜中，并跨越两个质膜之间的间隙延伸，形成间隙连接。与天然间隙连接通道类似，合成通道可以介导细胞间信号耦合和活性氧物质传递，导致细胞活动。
