复旦大学侯军利团队构建人工间隙连接介导细胞间信号和物质运输。相关研究成果发表在2024年4月24日出版的《自然—化学》。
天然间隙连接是一种负责细胞间信号传导和大规模通信的通道蛋白。然而，这些蛋白质的应用范围是有限的，因为它们不能大规模制备，也不能在体外自发插入细胞膜。人工间隙连接的构建可能为制备天然蛋白质的类似物，和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。
该文中，研究人员展示了由交替排列的带正电荷和带负电荷的柱[5]芳烃基序组成的，单分子管状分子构建的人工间隙连接通道。这些分子具有疏水-亲水-疏水三嵌段结构，使它们能够有效地插入两个相邻的质膜中，并穿过两个膜之间的间隙形成间隙连接。与天然间隙连接通道类似，合成通道可以介导细胞间信号偶联和活性氧的传递，从而导致细胞活性。
天然缝隙连接类似物的构建将为合成细胞构建细胞间通信途径提供自下而上的策略。现在，通过模拟天然连接通道的疏水-亲水-疏水三嵌段结构，研究人员从单分子管状通道制备了人工细胞间隙连接。
附：英文原文
Title: Constructing artificial gap junctions to mediate intercellular signal and mass transport
Author: Fu, Yong-Hong, Hu, Yi-Fei, Lin, Tao, Zhuang, Guo-Wei, Wang, Ying-Lan, Chen, Wen-Xue, Li, Zhan-Ting, Hou, Jun-Li
Issue&Volume: 2024-04-24
Abstract: 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. The construction of analogues of natural gap junctions would provide a bottom–up strategy for building intercellular communication pathways for synthetic cells. Now artificial intercellular gap junctions have been prepared from unimolecular tubular channels by mimicking the hydrophobic–hydrophilic–hydrophobic triblock structure of natural junction channels.
DOI: 10.1038/s41557-024-01519-8
