A team headed by Arizona State University chemistry professors Thomas Moore and Devens Gust has developed a light-powered molecular pump that shuttles calcium ions through a phospholipid membrane - calcium ion pumping that resembles various key cellular activities in living organisms, but engineered to be powered by light through specially designed molecules.
The research is reported in the November 28 issue of the journal Nature by Ira M. Bennett, Hebe M. Vanegas Farfano, Federica Bogani, Alex Primak, Paul A. Liddell, Ana L. Moore, Thomas A. Moore and Gust from Arizona State University and Luis Otero, Leonides Sereno and Juana J. Silber from Universidad National de Rio Cuarto in Argentina.
Beginning with an artificial membrane composed of a bilayer of phopholipids (similar to the lipid bilayers that form the membranes of living cells), the team created "shuttle" molecules that were soluble inside the lipid layer of the membrane, but not in the water inside and outside the "cell." These molecules, through the addition or removal of electrons, bind calcium ions at the outside surface of the liposome (these ions are water soluble and not ordinarily able to enter the oily lipid environment of the membrane), take them across the membrane, and release them at the membrane's inner surface. The ions, which cannot remain in the lipid environment, go to the water solution inside the cell, raising its concentration of calcium ions.
The operation is controlled by an "artificial reaction center" molecule (modeled after similar natural molecules used in the biological process of photosynthesis) which is directionally positioned across the membrane and donates and reabsorbs electrons at its opposite ends in response to light.
"The net result is the use of light energy to transfer calcium to the interior of the liposome," said Gust. "In lay terms, the shuttle molecule is like a taxicab that transports the calcium ion across town. The artificial reaction center is the engine that powers the taxicab, closing and opening its doors, and the light is the fuel that makes that happen."
In essence, light energy is transferred to the artificial reaction center molecule and is passed along and finally stored chemically in the increased concentration of calcium ions inside the artificial cell.
"The concentration of ions inside biological membranes is the central organizing feature of living cells, " explained Moore. "In living cells, if the key ions were allowed to come to equilibrium with their concentrations outside, then the cells would be dead. The cell requires the maintenance of an ion gradient across its borders to be considered a living cell. It's of interest to us to explore ways to generate this gradient - to pump these ions across artificial cells. This way, from the standpoint of energetics, we can drive reactions that are unique to living cells."
In a basic sense, an ion pump in an artificial cell is like a powerplant that drives the cell's "motor."
"This is an elaboration of a principle in biochemistry that underpins all bioenergetics," said Moore. "There's a good analogy with electricity - you make a voltage difference across a wire and the electrons run down it and you can extract work from that. Voltage is electro-motive force. A membrane with a difference in chemical potential across it would be like two wires going to a motor."
What could such a cellular machine be used for?
"One of the ideas would be to take a liposome, which is a nano-scale device, and use it as a nanofactory," Gust said. "You could put chemicals inside it, they would undergo reactions, and then you would take out the products. If you're going to do that, you need to have a way to transport the reactants into the liposome, and you need to have a way to transport the products back out--this kind of pump could, in principle, be used for that type of thing, with light as the controlling factor."
There are also a host of potential biomedical and other applications for both the specific and the general concept.
"In nature, there aren't pumps for calcium that work like ours, but the pumping of calcium across membranes is a really important function in biology," Gust said. "In muscle function, for example, a large fraction of the energy that is used pushes calcium ions across membranes. It's also important in vision, in nerve function...it's important in almost everything.
"Calcium release across membranes also has some role, not yet completely understood, in immune response in rheumatoid arthritis. We were funded for part of this work by the Harrington Arthritis Center because of that. We were also funded by the Department of Energy because of the relevance of this in transferring solar into chemical energy."
Gust and Moore note that this project and related research efforts in nanotechnology at ASU are outgrowths of more than a decade of research work done at ASU's Center for the Study of Early Events in Photosynthesis.
"The paradigms for nanotechnology almost all come from biology," said Moore. "The things we emulate are ready-built. We have to figure out how they work, take the basic principles out of them, throw away all the parts that are only important to evolutionary biology, and get down to the nuts and bolts, gears and wheels of how they work. As we have come to understand them, we can take these things and learn to adapt them for our own human purposes."
Sources: Devens Gust, 480-965-4430
Thomas Moore, 480-965-3308