Nanostructures: Visualizing Biological Networks in 4D


Photo: DNA-Nanostructures

A DNA structure as seen through the 4D electron microscope invented at Caltech; © Caltech/Zewail and Lorenz

Scientists at the California Institute of Technology have recently developed techniques for visualizing the behavior of biological nanostructures in both space and time, allowing them to measure the structure's stiffness.

"This type of visualization is taking us into domains of the biological sciences that we did not explore before," says Ahmed Zewail, Professor of Chemistry and professor of physics at the California Institute of Technology (Caltech). "We are providing the methodology to find out the stiffness of a biological network that has nanoscale properties." In biological nanostructures, like DNA networks, it has been difficult to measure stiffness, which is essential to their properties and functions.

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.

The researchers 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. "In nature, the behavior of matter is determined by its structure—the arrangements of its atoms in the three dimensions of space—and by how the structure changes with time, the fourth dimension," explains Zewail.

Zewail developed femtochemistry, which uses ultrashort laser flashes to observe fundamental chemical reactions occurring at the timescale of the femtosecond (one millionth of a billionth of a second). Although femtochemistry can capture atoms and molecules in motion, giving the time dimension, it cannot concurrently show the dimensions of space, and thus the structure of the material. This is because it utilizes laser light with wavelengths that far exceed the dimension of a nanostructure, making it impossible to resolve and image nanoscale details in tiny physical structures such as DNA.

To overcome this major hurdle, 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 picometers, or 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 or longer.

Using 4D electron microscopy, Zewail's group has begun to visualize protein assemblies called amyloids, which are believed to play a role in many neurodegenerative diseases, and they are continuing their investigation of the biomechanical properties of these networks. He says that this technique has the potential for broad applications not only to biological assemblies, but also in the materials science of nanostructures.; Quelle: California Institute of Technology