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Watching Proteins Fold

From scopes that help premature babies breathe to techniques for imaging live neurons and beating hearts as they develop, the latest optical and laser technology being deployed in medicine and the biosciences will be on display at the Optical Society's (OSA) Annual Meeting, Frontiers in Optics (FiO), which takes place Oct. 11-15 at the Fairmont San Jose Hotel and the Sainte Claire Hotel in San Jose, Calif.

One of the most important biological actions is the folding and unfolding of protein molecules. But getting hold of single protein molecules is difficult, and monitoring their gymnastic gyrations is even more so. Scientists at Harvard University have produced new video-based "optical tweezers" techniques for doing just this, enabling ultra-precise measurements to be made in a way that is simple and effective. The current U.S. secretary of energy, Steven Chu, won a Nobel Prize for his contribution toward controlling atoms with laser beams inside an enclosed trap; he later pioneered the use of laser beams for actually holding tiny objects -- even biological molecules -- in place. The Harvard device is among the latest and most versatile use of this optical tweezers approach.

Wesley Wong of the Rowland Institute at Harvard and his colleagues have developed a unique optical tweezers system that uses a combination of interference imaging, light modulation and custom software algorithms to achieve the necessary resolution and stability to watch proteins fold. This system, which employs already-existing optical technology components, utilizes 3-D video tracking to measure the lengths of short molecular tethers with angstrom resolution (less than 1 billionth of a meter) and active feedback control for a force stability of femtoNewtons (10^-15 Newtons). Fluctuations can be glimpsed at rates faster than 100,000 frames per second -- all with inexpensive video-imaging. The act of protein folding is quantified by measuring the end-to-end distance of a single molecule while the strength of the tweezers' grip is varied.

The Wong group uses optical tweezers to study the behavior of single molecules under force in order to reveal the nanoscopic workings of biological systems. Together with their collaborators, they have used this approach to expose the molecular feedback mechanism behind the regulation of blood clotting and to determine the dynamic mechanical properties of spectrin, a structural molecule largely responsible for the amazing material properties of red blood cells. (Paper FWS1, High-Resolution, High-Stability, "High-Frequency Optical Tweezers Method with a Simple Video Camera" is at 1:30 p.m. Wednesday, Oct. 14).

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