Tokyo Tech researchers developed the first synthetic mechanosensitive sodium channel by using a newly-developed aromatic fluorinated amphiphilic cyclephane. The new ion channels display both “stimuli responsiveness”, and “selective Ion Transport” capabilities. open new doorsFor the future industrial and therapeutic use of synthetic mechanosensitive channel.
Nature inspires humanity in many different ways. Consider, for example, “stimuliresponsive” ion-transport channel proteins. These proteins are embedded within cell membranes and respond to various external stimuli such as light, pH and mechanical force. Researchers have tried to create artificial versions of channel proteins in order to use them in industrial and therapeutic settings. But, it has not been easy to synthesize them. They are difficult to synthesize due to their complicated structural requirements, which include specific ion transportation properties and stimuli responsiveness.
These difficulties were overcome by researchers at Tokyo Institute of Technology (Tokyo Tech), under the leadership of Assistant Professor Kohei Sato (full Professor Kazushi Kinbara) who have developed the first synthetic mechanosensitive channel (responsive to mechanical force) with potassium ion selectivity. Their findings have been published in the Journal of the American Chemical Society. Assist. Professor Sato and Professor Kinbara are both affiliated with Tokyo Institute of Technology (Tokyo Tech). They say that “With our experience designing multiblock amphiphiles that self-assemble to form supramolecular Ion Channels, we hypothesized linear amphiphiles weren’t suitable for transporting certain ions.” Therefore, they attempted structural modifications to include both stimuli responsiveness and selectivity.
Assist. Professor. Sato and Prof. Kinbara altered the structure of an organic compound known as a multiblock molecule to incorporate a perfluorinated Aroma unit. The resulting structure, a fluorinated amphiphilic cyclophane, contained hydrophobic perfluorinated oligo(phenylene-ethynylene) units and hydrophilic octa(ethylene glycol) linkers. For investigating the effects of aromatic fluorination, researchers also created one fluorinated and one unfluorinated amphiphilic cyclephane.
Microscopy revealed both the perfluorinated and perfluorinated Cyclophane (named C) were visible.FF,The partially fluorinated cyclophane C, also known asFHThe lipid bilayer membrane could be incorporated with the fluorinated cyclophane, but not the nonfluorinated one. The researchers examined C’s ion transport, stimuli responsiveness, as well as potassium ion selectivity.FFCFHFluorescence assays and conductance measurements were used. They found that both CFFCFHThey self-assembled within the bilayer membrane to form supramolecular electron channels. The transmembrane CION transport property was confirmed by the flow of current across membrane.FFCFHC is more efficient and more prominent.FF.
The channels created by C were also confirmed to be responsive to stimuli via changes in current flow upon applying membrane tensionFFCFH. C is the ion transport propertyFFC was not affected much, although it was significantly affected.FH. Assist. Assist.FHCFFWithin the membrane.
Finally, the fluorescence assay showed highest permeability of CFFFor potassium ions, compared to other alkali-metal cations. This was due to the greater affinity of potassium ions to the fluorine-atoms in the structure’s core.
Assist. Prof. Sato, Prof. Kinbara said that “The fact C formed a supramolecular Ion Channel”FFSuch stimuli responsiveness and potassium selectivity are not only fascinating, but also strikingly like the mechanosensitive channels found within mammalian neurons.
These demonstrations open up possibilities for the development of treatments for ion-channel-related diseases, manipulation of biological processes, and industrial material purification technologies.