Scientists at the University of Stuttgart have made a groundbreaking advancement in synthetic biology by using DNA origami to control the structure and function of biological membranes. This innovative system has the potential to revolutionize drug delivery, offering a new way to efficiently transport large therapeutic molecules into cells, thereby paving the way for more targeted and precise treatments. The research, led by Professor Laura Na Liu and published in Nature Materials, marks a significant milestone in the application of DNA nanotechnology for medical and biological applications.
A cell’s shape and structure are integral to its biological function, embodying the principle of “form follows function.” This idea is not only prevalent in modern architecture but also fundamental in understanding cellular mechanics. In synthetic biology, mimicking this principle in artificial cells has proven to be a considerable challenge. However, the recent progress in DNA nanotechnology has provided a solution, enabling scientists to design transport channels that are large enough to carry therapeutic proteins across cell membranes.
Professor Laura Na Liu, Director of the 2nd Physics Institute at the University of Stuttgart and Fellow at the Max Planck Institute for Solid State Research, has led the development of a novel tool for controlling the shape and permeability of lipid membranes in synthetic cells. These artificial membranes, composed of lipid bilayers, mimic biological membranes and are useful for studying membrane dynamics, protein interactions, and lipid behavior.
The research team’s work represents a significant milestone in the application of DNA nanotechnology to regulate cell behavior. The project centers on giant unilamellar vesicles (GUVs)—cell-sized, simple structures that mimic living cells. Using DNA nanorobots, the researchers were able to influence the shape and functionality of these synthetic cells. These DNA-based robots are designed to interact with their environment in a controlled and programmable manner, allowing for precise adjustments in the membrane’s behavior.
Professor Liu described the work as a key development in the field: “This work is a milestone in the application of DNA nanotechnology to regulate cell behavior.” By programming these nanorobots, Liu’s team was able to influence the shape of GUVs and create synthetic channels in their membranes. These channels were large enough to allow therapeutic molecules, such as proteins and enzymes, to pass through, a critical step in advancing targeted drug delivery systems.
DNA nanotechnology is a primary focus of Professor Liu’s research, particularly DNA origami structures. DNA origami refers to DNA strands folded into specific shapes using short DNA sequences known as staples. Liu’s team leveraged these DNA origami structures to create reconfigurable nanorobots that could reversibly change shape and influence their surroundings at the micrometer scale.
The team discovered that the transformation of these DNA nanorobots could trigger changes in the GUVs, causing the formation of synthetic channels in the lipid membranes. These channels enabled large molecules to pass through, and could be resealed if necessary. This innovative method allows the creation of functional, artificial structures that can operate within biological environments.
Professor Stephan Nussberger, a co-author of the study, explained, “This means that we can use DNA nanorobots to design the shape and configuration of GUVs to enable the formation of transport channels in the membrane.” Nussberger also pointed out the significance of the finding: “It is extremely exciting that the functional mechanism of the DNA nanorobots on GUVs has no direct biological equivalent in living cells.” This suggests that synthetic platforms, such as DNA nanorobots, could potentially function in biological environments with less complexity than their biological counterparts.
The study opens up new possibilities for therapeutic strategies. The system developed by Liu and her team creates cross-membrane channels that can efficiently transport specific molecules into cells. Crucially, these channels can be programmed to close when needed, offering precise control over the flow of therapeutic agents.
When applied to living cells, this system could facilitate the targeted delivery of therapeutic proteins or enzymes, ensuring they reach their intended cellular destinations. This approach could significantly improve the effectiveness of drug delivery systems, providing a more controlled and less invasive method for treating diseases.
Professor Hao Yan, another co-author of the study, emphasized the potential impact of this research: “Our approach opens up new possibilities to mimic the behavior of living cells. This progress could be crucial for future therapeutic strategies.”
In summary, the use of DNA origami to create programmable transport channels in synthetic cell membranes represents a significant step forward in the field of synthetic biology. This breakthrough not only advances our understanding of cellular mechanisms but also provides a powerful tool for the efficient delivery of therapeutic molecules, offering exciting possibilities for future treatments.
By Impact Lab