Researchers at Johannes Gutenberg University Mainz (JGU), the Max Planck Institute for Polymer Research and the University of Texas at Austin have identified a form of molecular motion that has not previously been observed. When what are known as 'guest molecules' – molecules that are accommodated within a host molecule – penetrate droplets of DNA polymers, they do not simply diffuse in them in a haphazard fashion, but propagate through them in the form of a clearly-defined frontal wave. "This is an effect we did not expect at all," points out Weixiang Chen of the Department of Chemistry at JGU, who played a major role in the discovery. The findings of the research team have today been published in an article in the prestigious journal Nature Nanotechnology. The new insights are not only fundamental to our understanding of how cells regulate signals, but they could also contribute to the development of intelligent biomaterials, innovative types of membranes, programmable carriers of active ingredients and synthetic cell systems able to imitate the organizational complexity of the processes in living beings.

It is usually the case that molecules are distributed throughout liquids by means of simple diffusion. For instance, if you add a blue dye to a glass of water, the dye gradually disperses in the liquid, forming soft, blurry color gradients. However, the observed behavior of guest molecules in DNA droplets is quite different. "The molecules move in a structured and controlled manner that is contrary to the traditional models, and this takes the form of what appears to be a wave of molecules or a mobile boundary," explains Professor Andreas Walther from JGU's Department of Chemistry, who led the research project.

The research team used droplets made up of thousands of individual strands of DNA, structures that are also known as biomolecular condensates. What is of particular interest in this connection is the fact that the properties of the droplets can be precisely determined with the help of the DNA structures and other parameters, such as the concentration of salts. Moreover, these droplets have their counterparts in biological cells, which are able to employ similar condensates to arrange complex biochemical processes without the need for membranes. "Our synthetic droplets thus represent an excellent model system with which we can simulate natural processes and come to better understand them," emphasizes Chen. Into their droplets, the researchers introduced specially designed 'guest' DNA strands that are able to specifically recognize the inner structure of the droplets and bind to them. According to the team, the intriguing motion of the guest molecules, that they have now detected for the first time, is in part attributable to the way that the added DNA and the DNA present in the droplets combine on the basis of the key-and-lock principle. This means that the surrounding material becomes less dense and no longer fixed in place, so that swollen, dynamic states develop locally. Chen adds: "The well-defined, highly concentrated front continues to move forward in a linear fashion over time, driven by chemical binding, material conversion and programmable DNA interactions. Something that is completely new when it comes to soft matter."

The findings are not only relevant to providing us with a better understanding of the physics of soft matter, but also to improving our knowledge of the chemical processes that occur in cells. "This might be one of the missing pieces of the puzzle that, once assembled, will reveal to us how cells regulate signals and organize processes on the molecular level," states Walther. This would also be of interest when it comes to the treatment of neurodegenerative disorders in which proteins migrate from cell nuclei into the cytoplasm, forming condensates there. As these age, they transform from a dynamic to a more stable state and build the problematic fibrils. "It is quite conceivable that we may be able to find a way of influencing these aging processes with the aid of our new insights, so that, over the long term, an entirely new approach to the treatment of neurodegenerative diseases could emerge," concludes Walther.