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Weighing—and Imaging—Molecules One at a Time

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Multimode nanoelectromechanical systems (NEMS) based mass sensor; the main figure schematically depicts a doubly-clamped beam vibrating in fundamental mode (1). Conceptual “snapshots” of the first six vibrational modes are shown below (1-6), colors indicate high (red) to low (blue) strain. The inset shows a colorized electron micrograph of a piezoelectric NEMS resonator fabricated in Caltech’s Kavli Nanoscience Institute. Image Credit: M. Matheny, L.G. Villanueva, P. Hung, J. Li and M. Roukes/Caltech

Building on their creation of the first-ever mechanical device that can measure the mass of individual molecules, one at a time, a team of Caltech scientists and their colleagues have created nanodevices that can also reveal their shape. Such information is crucial when trying to identify large protein molecules or complex assemblies of protein molecules. "You can imagine that with large protein complexes made from many different, smaller subunits there are many ways for them to be assembled. These can end up having quite similar masses while actually being different species with different biological functions. This is especially true with enzymes, proteins that mediate chemical reactions in the body, and membrane proteins that control a cell's interactions with its environment," explains Michael Roukes, the Robert M. Abbey Professor of Physics, Applied Physics, and Bioengineering at Caltech.   With their devices, Roukes and his colleagues can measure the mass of an individual intact molecule. Each device—which is only a couple millionths of a meter in size or smaller—consists of a vibrating structure called a nanoelectromechanical system (NEMS) resonator. When a particle or molecule lands on the nanodevice, the added mass changes the frequency at which the structure vibrates, much like putting drops of solder on a guitar string would change the frequency of its vibration and resultant tone. The induced shifts in frequency provide information about the mass of the particle. But they also, as described in the new paper, can be used to determine the three-dimensional spatial distribution of the mass: i.e., the particle's shape.