Are You Ready for 4D?

Every great structure, from the Empire State Building to the Golden Gate Bridge, depends on specific mechanical properties to remain strong and reliable. Rigidity—a material’s stiffness—is of particular importance for maintaining the robust functionality of everything from colossal edifices to the tiniest of structures. In biological nanostructures, like DNA networks, it has been difficult to measure this stiffness, which is essential to their properties and functions. But scientists at the California Institute of Technology (Caltech) have recently developed techniques for visualizing the behavior of biological nanostructures in both space and time, allowing them to directly measure stiffness and map its variation throughout the network.

Nobel Laureate Ahmed Zewail, the Linus Pauling Professor of Chemistry and professor of physics at Caltech, who coauthored a paper with Ulrich Lorenz, a postdoctoral scholar in Zewail’s lab, were able to see for the first time the motion of DNA nanostructures in both space and time using the four-dimensional (4D) electron microscope developed at Caltech’s Physical Biology Center for Ultrafast Science and Technology.

The 4D electron microscope employs a stream of individual electrons that scatter off objects to produce an image. The electrons are accelerated to wavelengths of trillionths of a meter, providing the capability for visualizing the structure in space with a resolution a thousand times higher than that of a nanostructure, and with a time resolution of femtoseconds (one millionth of one billionth, of a second ) or longer.

4D electron microscopy F5.large
The conceptual design of Caltech’s 4D Microscopy is presented on the right. Shown on the left are typical UEM frames of real-space images and diffraction patterns, together with three-dimensional maps of femtosecond-resolved electron-energy-loss spectra (FEELS).

The experiments begins with a structure created by stretching DNA over a hole embedded in a thin carbon film. Using the electrons in the microscope, several DNA filaments were cut away from the carbon film so that a three-dimensional, free-standing structure was achieved under the 4D microscope.

DNA Structure 130211135013-large

Next, the scientists employed laser heat to excite oscillations in the DNA structure, which were imaged using the electron pulses as a function of time—the fourth dimension. By observing the frequency and amplitude of these oscillations, a direct measure of stiffness was made.

Knowing the mechanical properties of DNA structures is crucial to building sturdy biological networks, among other applications. According to Zewail, this type of visualization of biomechanics in space and time should be applicable to the study of other biological nanomaterials, including the abnormal protein assemblies that underlie diseases like Alzheimer’s and Parkinson’s.




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