Conformational switching for trans-membrane communication

细胞被一层不透水的膜包围着，生命系统面临的挑战之一是如何通过这层膜将信息进出细胞。科学家们也面临着同样的挑战，他们试图利用人造细胞或囊泡来理解细胞行为，这些细胞或囊泡可以用作微型化学反应器或转运体。细胞通过在膜上制造通道来传导离子来解决这个问题，或者通过装配一种“钟拉”系统来解决这个问题，在这种系统中，细胞外表面的一个调整会导致内部表面分子形状的改变。后一种方法从未在合成系统中实现，尽管最近化学家可以使用具有明确形状的合适分子，称为“文件夹”。我们现在计划将这些文件夹用作通过人造细胞膜的信息交流器（“换能器”）。要做到这一点，我们必须开发出在文件夹两端输入和读出信息的方法。首先，这将在溶液中完成，然后我们将把我们发现的转移到囊泡的膜上。我们将开发研究和控制膜中分子形状的方法，然后在此基础上构建信号方法，使囊泡内发生的化学反应受到外部介质中的化学信息的控制。这些细胞行为的人工类似物将极大地简化那些希望了解细胞内细胞通讯的化学基础的生物科学家所面临的挑战。我们也可以把这些囊泡用作微型可控反应堆，或者找到方法让它们在可控的时间或地点释放它们的内容物。此外，我们计划构建的这些分子与“peptaibol”类抗生素有很多共同之处，我们的研究可能会提供具有可控功能的替代合成抗生素。

Cells are surrounded by an impermeable membrane, and one of the challenges living systems face is how to communicate information into and out of the cell through that membrane. The same challenges face scientists seeking to understand cellular behaviour using artificial cells, or vesicles, which can be used as miniature chemical reactors or transporters. Cells solve the problem either by making channels through the membrane which can conduct ions, or by rigging up a type of 'bell-pull' system, in which a tweak at the external surface of the cell leads to a change in shape of a molecule on the internal surface. This latter method has never been realised in a synthetic system, despite suitable molecules with well defined shapes, known as 'foldamers', recently becoming available to chemists. We now plan to put these foldamers to use as communicators ('transducers') of information through an artificial cell membrane. To do this we will have to develop ways of making them and of inputting and reading out information at opposite ends of the foldamer. Firstly, this will be done in solution, and then we will transfer what we discover to the membranes of vesicles. We will develop ways of studying and controlling the shape of molecules in membranes, and then build on this to construct signalling methods which allow the chemistry happening inside the vesicle to be controlled by chemical messages in the outer medium. These artificial analogues of cellular behaviour will greatly simplify the challenges presented to bioscientists wishing to understand the chemical basis of cellular communication in cells. We can also use these vesicles as miniature controllable reactors, or work out ways of making them release their contents at a controlled time or at controlled locations. Furthermore these molecules we plan to build have much in common with the 'peptaibol' class of antibiotics, and our research may give alternative, synthetic antibiotics with controllable function.