CELL BIOLOGY: Unprecedented dynamics measurement with 3-D plasmon rulers

Three-dimensional plasmon rulers, developed by a multinational research team, promise to reveal in unprecedented detail such biologic events as the interaction of DNA with enzymes, protein folding, peptide motion, and cell membrane vibration.

Based on coupled plasmonic oligomers in combination with high-resolution plasmon spectroscopy, the approach “enables us to retrieve the complete spatial configuration of complex macromolecular and biological processes,” and to track their dynamic evolution, says Paul Alivisatos, director of U.S. Department of Energy’s Lawrence Berkeley National Laboratory, who led the team of scientists at Berkeley Lab and the University of Stuttgart, Germany.

According to Alivisatos, two noble metallic nanoparticles in close proximity will couple through their plasmon resonances to generate a light-scattering spectrum that depends strongly on the distance between them. This effect has enabled linear plasmon rulers to measure nanoscale distances in cells.

Compared to other types of molecular rulers, based on chemical dyes and fluorescence resonance energy transfer (FRET), plasmon rulers do not blink or photobleach, and offer exceptional photostability and brightness—but until now could measure distances only along one dimension.

According to researcher Laura Na Liu, the key to success was the ability “to create sharp spectral features in the otherwise broad resonance profile of plasmon-coupled nanostructures by using interactions between quadrupolar and dipolar modes.” Typical dipolar plasmon resonances are broad because of radiative damping, and the simple coupling between multiple particles produces indistinct spectra not easily converted into distances. She and her co-authors overcame this problem with a 3-D ruler constructed from five gold nanorods of individually controlled length and orientation, in which one nanorod is placed perpendicular between two pairs of parallel rods to form a structure that resembles the letter H.

“The strong coupling between the single nanorod and the two parallel nanorod pairs suppresses radiative damping and allows for the excitation of two sharp quadrupolar resonances that enable high-resolution plasmon spectroscopy,” Liu says. “Any conformational change in this 3-D plasmonic structure will produce readily observable changes in the optical spectra.”

The spatial freedom afforded its five nanorods also enables determination of the direction and magnitude of structural changes.

The scientists envision that 3-D plasmon rulers could attach, through biochemical linkers, to a sample macromolecule, for example, to various points along a strand of DNA or RNA—or at different positions on a protein or peptide. The sample macromolecule would then be exposed to light and the optical responses of the 3-D plasmon rulers would be measured via dark field microspectroscopy.

1. N. Liu et al., Science 332 (6036), 1407–10 (2011).