Composite Synthetic Membranes Containing Native and Engineered Transport Proteins

Our membrane transport protein laboratory has worked with material scientists, computational chemists and electrical and mechanical engineers to design bioactuators and sensing devices. The group has demonstrated that it is possible to produce materials composed native and engineered biological transport proteins in a variety of synthetic porous and solid materials. Biological transport proteins found in nature include pumps, which use energy to produce gradients of solutes, ion channels, which dissipate ion gradients, and a variety of carriers which can either transport substances down gradients or couple the uphill movement of substances to the dissipation of gradients. More than one type of protein can be reconstituted into the membranes to allow coupling of processes such as forming concentration gradients with ion pumps and dissipating them with an ion channel. Similarly, ion pumps can provide ion gradients to allow the co-transport of another substance. These systems are relevant to bioactuation. An example of a bioactuator that has recently been developed in the laboratory was based on a sucrose-proton exchanger coupled to a proton pump driven by ATP. When coupled together, the net reaction across the synthetic membrane was ATP driven sucrose transport across a flexible membrane across a closed space. As sucrose was transported, net flow of water occurred, causing pressure and deformation of the membrane. Transporters are regulated in nature. These proteins are sensitive to voltage, pH, sensitivity to a large variety of ligands and they can be modified to gain or lose these responses. Examples of sensors include ligand gated ion channels reconstituted on solid and permeable supports. Such sensors have value as high throughput screening devices for drug screening. Other sensors that have been developed in the laboratory include sensors for membrane active bacterial products such as the anthrax pore protein. These materials can be self assembled or manufactured by simple techniques, allowing the components to be stored in a stable form for years before (self) assembly on demand. The components can be modified at the atomic level, and are composed of nanostructures. Ranges of sizes of structures using these components range from the microscopic to macroscopic scale. The transport proteins can be obtained from natural sources or can be produced by recombinant methods from the genomes of all kingdoms including archea, bacteria and eukaryotes. For example, the laboratory is currently studying an ion channel from a thermophile from deep sea vents which has a growth optimum of 90 degrees centigrade, and has membrane transport proteins with very high temperature stability. The transport proteins can also be genetically modified to produce new properties such as activation by different ligands or transport of new substances such as therapeutic agents. The structures of many of these proteins are known, allowing computational chemists to help understand and predict the transport processes and to guide the engineering of new properties for the transport proteins and the composite membranes. Supported by DARPA and USARMY MURI Award and AFOSR.