Scientists have made significant strides in manipulating the structure and functionality of biological membranes using ‘DNA origami’. The innovative system they created may enhance the delivery of large therapeutic agents into cells, marking a breakthrough for targeted drug delivery and other therapeutic techniques. This development represents a useful addition to the synthetic biology toolkit.
Researchers from the University of Stuttgart have effectively controlled the structure and functionality of biological membranes through “DNA origami.” Their newly developed system could improve the transport of large therapeutic loads into cells, providing a fresh approach for precise medication delivery and additional therapeutic methods. This advancement enriches the resources available in synthetic biology. The findings were detailed by Prof. Laura Na Liu and her team in the journal Nature Materials.
The shape and form of a cell are crucial for its biological functions. This reflects the concept of “form follows function,” a principle widely recognized in modern design and architecture. Adapting this principle for artificial cells presents a challenge within synthetic biology. However, progress in DNA nanotechnology provides promising solutions by enabling the creation of new transport channels that are sufficiently large to allow therapeutic proteins to cross cell membranes. Scientists like Prof. Laura Na Liu, who leads the 2nd Physics Institute at the University of Stuttgart and is a Fellow at the Max Planck Institute for Solid State Research (MPI-FKF), have developed innovative tools to manage the shape and permeability of lipid membranes found in synthetic cells. These membranes are created from lipid bilayers enclosing a water space, serving as simplified models of biological membranes that help study the dynamics of membranes, protein interactions, and lipid behavior.
A breakthrough in the use of DNA nanotechnology
This novel tool holds promise for creating functional synthetic cells. Laura Na Liu’s research seeks to significantly impact the development of new therapeutic strategies. Her team has achieved the use of signal-dependent DNA nanorobots to create programmable interactions with synthetic cells. “This work marks a significant milestone in employing DNA nanotechnology to modulate cell behavior,” states Liu. The researchers utilize giant unilamellar vesicles (GUVs), simple, cell-sized structures mimicking living cells. Through DNA nanorobots, they influenced both the shape and functionality of these synthetic cells.
Creating new transport channels for proteins and enzymes
DNA nanotechnology is a key focus of Laura Na Liu’s research. She specializes in DNA origami structures, which involve folding DNA strands using specifically designed short DNA sequences known as staples. Liu’s team harnessed these DNA origami structures as reconfigurable nanorobots capable of changing shape, thus affecting their surroundings at the micrometer level. The team’s results showed that these nanorobot transformations could lead to alterations in the GUVs’ shape and the generation of synthetic channels in the model GUV membranes. These channels enable large molecules to traverse the membrane and can be sealed off if necessary.
Completely artificial DNA structures in biological contexts
“This reveals our ability to use DNA nanorobots to design GUVs’ shape and configuration, facilitating the development of transport channels in the membrane,” remarks Prof. Stephan Nussberger, a co-author of the study. “It’s thrilling that the functional mechanism of these DNA nanorobots on GUVs does not have an exact biological counterpart in living cells,” adds Nussberger.
The new research prompts further inquiries: Is it possible to design synthetic platforms, such as DNA nanorobots, with less complexity than their biological equivalents while still functioning effectively in biological environments?
Gaining insights into disease mechanisms and enhancing therapies
This study is a significant advancement towards that goal. The cross-membrane channel system produced by DNA nanorobots allows efficient transport of specific molecules into cells. Notably, these channels are large and can be programmed to close when necessary. When applied to living cells, this system can improve the delivery of therapeutic proteins or enzymes to targeted locations within the cell, providing new avenues for medication administration and other therapeutic approaches. “Our method opens up exciting possibilities for emulating the behavior of living cells. This advancement could be pivotal for future therapeutic strategies,” concludes Prof. Hao Yan, another co-author of the study.
