A novel imaging method developed at the University of Oregon may help researchers better understand and predict how nanometer-size pieces fit together into structures ranging from living cells to artificially fabricated devices. Coupling laser-driven, two-dimensional fluorescence imaging and high-performance computer modeling, a six-member team led by Andrew H. Marcus of the University of Oregon and Alan Aspuru-Guzik of Harvard University solved the conformation of self-assembled porphyrin molecules in a biological membrane. Porphyrins are organic compounds that are ubiquitous in living things. They carry mobile electrical charges that can hop from molecule to molecule and allow for nanoscale communications and energy transfer. They also are building blocks in nanodevices. Andrew H. Marcus is a professor of chemistry at the University of Oregon. (Photo: University of Oregon) The new technique — phase-modulation 2-D fluorescence spectroscopy — is detailed in a paper scheduled to appear this week in the online edition of Proceedings of the National Academy of Sciences. The breakthrough skirts the often-needed step of obtaining crystals of molecules that are being studied, Marcus said. Most functional biological molecules don't easily form crystals. "Our technique is a workable way to determine how macromolecular objects assemble and form the structures they will in biological environments," he added. "It's robust and will provide a means to study biological protein-nucleic acid interactions." Work already is under way to modify the experimental instrumentation to apply it to DNA replication machinery — one category of the best-known macromolecular complexes, which consist of nucleic acids and proteins that must be properly aligned to function correctly. "It's a strategy that will allow us to do two things: Look at these complexes one molecule at a time, and perform experiments at short ultraviolet wavelengths to look at DNA problems," Marcus said. In addition, the approach should be useful to materials scientists striving to understand and harness the necessary conformation of polymers used in the production of nanoscale devices. "In biology, large molecules assemble to form very complex structures that all work together like a machine," he said. "The way these nanoscale structures form and become functional is an actively pursued question." The technique builds on earlier versions of 2-D optical spectroscopy that emerged in efforts to get around limitations involved in applying x-ray crystallography and nuclear magnetic resonance to such research. The previous 2-D approaches depended on the detection of transmitted signals but lacked the desired sensitivity. For more information, visit: http://chemistry.uoregon.edu