Cryoforce Spectroscopy Reveals DNA Mechanical Properties

Physicists from the University of Basel have developed a low temperature method to examine the elasticity and binding properties of DNA molecules. The process utilized cryoforce spectroscopy and computer simulations, a combination that revealed DNA molecules behaving like a chain of small coil springs.

DNA is not only a popular research topic but can also be used within DNA origami, according to the team. The process involves manipulating genetic material in such a way that folding DNA strands creates small two- and three-dimensional structures potentially used as containers for pharmaceutical substances, conductive tubes or highly sensitive sensors.

The structure, elasticity and binding force of DNA components must be understood in order to form any desired shape, according to the team, but such physical parameters cannot be measured at room temperature because molecules are constantly in motion. The researchers thus turned to low temperatures, using cryoforce microscopy for the first time to characterize DNA molecules and examine binding forces and elasticity.

The process involved placement of nanometer long DNA strands that contained 20-cytosine nucleotides on a gold surface. At a temperature of 5K, one end of the DNA strand was then pulled upwards using the tip of an atomic force microscope. Individual components of the strand then freed themselves from the surface little by little, allowing the physicists to record elasticity as well as the forces required to detach the DNA molecules from the gold surface.

“The longer the detached piece of DNA, the softer and more elastic the DNA segment becomes,” says Dr. Rémy Pawlak, lead author of the team’s research published in Nature Communications. He emphasized that individual components of the DNA behave like a chain of multiple coil springs connected to one another, allowing the researchers to determine the spring constant for individual DNA components.

Computer simulations also clarified that the DNA detached discontinuously from the surface. This situation is linked not only to the breaking up of bonds between the cytosine bases and the DNA backbone from the gold surface, but also their abrupt movements over the gold surface. The theoretical elasticity values correlate very closely with the experiments and confirm the model of serially arranged springs.

Such studies confirmed that cryoforce spectroscopy is very well suited to examining the forces, elasticity and binding properties of DNA strands on surfaces at low temperatures. “As with cryogenic electron microscopy, we take a snapshot with cryoforce spectroscopy, which gives us an insight into the properties of DNA,” says Ernst Meyer, team leader and professor from the Swiss Nanoscience Institute. “In [the] future, we could also make use of scanning probe microscope images to determine nucleotide sequences.”