LMU chemists present two studies that open new possibilities for biotechnological applications.
In the world of nanotechnology, the development of dynamic systems that respond to molecular signals is becoming increasingly important. The DNA origami technique, in which DNA is programmed to produce functional nanostructures, plays a key role in this. Teams led by LMU chemist Philip Tinnefeld have now published two studies showing how DNA origami and fluorescent probes can be used to release molecular cargo in a targeted manner.
In the news Angewandte Chemiethe researchers report on their development of a novel DNA origami-based sensor that can detect lipid vesicles and deliver molecular cargo to them with precision. The sensor works using single-molecule fluorescence resonance energy transfer (smFRET), which measures the distance between two fluorescent molecules. The system consists of a DNA origami structure, from which protrudes a single-stranded DNA, which is labeled at the tip with fluorescent dye. When the DNA comes into contact with vesicles, its conformation changes. This changes the fluorescent signal, because the distance between the fluorescent label and a second fluorescent molecule on the origami structure changes. This method allows vesicles to be detected.
Sensor is transmitted accurately
In a second step, the system can be used as a transport vehicle for molecules, with the sensor string serving as molecular cargo that can be transferred to the vesicle. By further adapting the system, the researchers were also able to accurately monitor the transhipment of the cargo.
Lipid vesicles play a key role in many cellular processes, such as molecular transport and signal transduction. As such, the ability to detect and manipulate them is of particular interest for biotechnological applications such as the development of targeted therapies. The approach outlined here could provide a way to load lipid nanoparticles with a precisely defined number of molecules in applications such as vaccines. “Our system also offers promising approaches for biological research when it comes to better understanding and controlling cellular processes at the molecular level,” says Tinnefeld.
Controllable conformational changes
In the second study, which was recently published in the journal Nature communicationa second team led by Tinnefeld and Yonggang Ke (Emory University, Atlanta, Georgia) presents a DNA origami structure that undergoes a stepwise allosteric conformational change when certain DNA strands bind. Using FRET probes, the researchers were able to monitor this process at the molecular level and show how the reaction steps can be temporarily controlled. Furthermore, they show how a DNA payload can be specifically released during this process, opening up new possibilities for controlled reaction cascades.
