Engineered Ion Channels on Synthetic Flexible Membranes: Ion Channel Devices With Focus on Peptides

Recent studies of engineered ion channels on synthetic flexible membranes realized unprecedented materials properties. Starting with ion channels of known sequence and crystal structures, these studies outlined the structural basis for functional and regulatory properties, and developed new computational tools capable of predicting structural and functional properties of the native ion channels as well as native or engineered ion channels that were similar in structure to each other. The approaches taken to prepare the engineered composite membranes and the computational tools are generally applicable to the development, design and prediction of properties of a wide variety of materials such as selectively permeable membranes or functionalized thin films with desired chemical, electrical or optical properties. ClC-2 Cl⁻ transporting channels and related ion channels were used for this work. The following major developments have facilitated this work. First, the X-ray crystal structure of a bacterial ClC Cl⁻ channel was published and our group has been able to use that information in computational studies to develop structures for ClC channels and their transport mechanisms. Recent NMR and X-ray crystal structural studies have given important new information regarding the structure of the intracellular region, and this information helps to explain the structural basis for our findings that this same region is involved in phosphorylation-dependent regulation of the channel. Dissection and reconstitution of this region has already been carried out, raising our level of confidence that we can exploit this regulatory region to develop sensors in future studies. The group was then able to remove those native or engineered ion channels from cells, and place these onto a wide variety of synthetic supports without loss of function. This effort produced unique new materials with the ability to “sense” the environment and at the same time send an electrical signal reporting changes in the chemical or physical environment. These devices can sense chemicals and toxins and even shrink and swell or produce electrical energy from biochemicals. Indeed, the work contributes to a new field of engineering for producing materials with unprecedented properties. These materials can sense and report on chemical, physical and electromagnetic changes in the environment. In living cells, these ion channels other chemi-osmotic transport proteins use electrochemical gradients formed by light and chemical substrates to produce and interconvert energy, mechanical work, electrical work, osmotic work, chemical work and heat. Guided by new predictive computational approaches, these composite materials will do the same.