The world’s tiniest plumbing may probably funnel medicine to particular person human cells.
Engaged on microscopic pipes only a millionth the width of a single strand of human hair, Johns Hopkins University researchers devised a way to guard these tiniest of pipelines towards even the smallest of leaks.
Leak-free pipe constructed of self-assembling, self-repairing nanotubes that may hyperlink to completely different biostructures is a large step towards creating a nanotube community which may sooner or later carry specialised medicine, proteins, and molecules to specified cells within the human physique. The extremely exact measurements have been lately outlined in Science Advances.
Leak-free piping made with nanotubes that self-assemble, self-repair, and may join themselves to completely different biostructures. This video shows these nanotubes “wiggling”. Credit score: Johns Hopkins College
“This examine suggests very strongly that it’s possible to construct nanotubes that don’t leak utilizing these straightforward strategies for self-assembly, the place we combine molecules in an answer and simply allow them to kind the construction we would like,” mentioned Rebecca Schulman, an affiliate professor of chemical and biomolecular engineering who co-led the analysis. “In our case, we will additionally connect these tubes to completely different endpoints to kind one thing like plumbing.”
The scientists used tubes that have been a number of microns lengthy, or roughly the scale of a mud particle, and had a diameter of seven nanometers, or about two million occasions smaller than an ant.
The know-how relies on an present approach that repurposes DNA fragments as building blocks to grow and repair the tubes while allowing them to seek out and connect to specific structures.
Similar structures have been created in earlier experiments to create smaller structures known as nanopores. These designs concentrate on DNA nanopores’ ability to regulate the transport of molecules through lab-grown lipid membranes that resemble cell membranes.
However, if nanotubes are like pipes, nanopores are like short pipe fittings that cannot reach other tubes, tanks, or equipment on their own. To solve these kinds of issues, Schulman’s team specializes in bio-inspired nanotechnology.
“Building a long tube from a pore could allow molecules not only to cross the pore of a membrane that held the molecules inside a chamber or cell but also to direct where those molecules go after leaving the cell,” Schulman said. “We were able to build tubes extending from pores much longer than those that had been built before that could bring the transport of molecules along nanotube ‘highways’ close to reality.”
The nanotubes form using DNA strands that are woven between different double helices. Their structures have small gaps like Chinese finger traps. Because of the extremely small dimensions, scientists had not been able to test whether the tubes could transport molecules for longer distances without leaking or whether molecules could slip through their wall gaps.
Yi Li, a doctoral graduate from Johns Hopkins’ chemical and biomolecular engineering department who co-led the study, performed the nano-equivalent of capping the end of a pipe and turning on a faucet to make sure no water leaks out. Yi capped the ends of the tubes with special DNA “corks,” and ran a solution of fluorescent molecules through them to track leaks and influx rates.
By precisely measuring the shape of the tubes, how their biomolecules connected to specific nanopores, and how fast the fluorescent solution flowed, the team demonstrated how the tubes moved molecules into tiny, lab-grown sacks resembling a cell’s membrane. The glowing molecules slid through like water down a chute.
“Now we can call this more of a plumbing system because we’re directing the flow of certain materials or molecules across much longer distances using these channels,” Li said. “We are able to control when to stop this flow using another DNA structure that very specifically binds to those channels to stop this transport, working as a valve or a plug.”
DNA nanotubes could help scientists gain a better understanding of how neurons interact with one another. Researchers could also use them to study diseases like cancer, and the functions of the body’s more than 200 types of cells.
Next, the team will conduct additional studies with synthetic and real cells, as well as with different types of molecules.
Reference: “Leakless end-to-end transport of small molecules through micron-length DNA nanochannels” by Yi Li, Christopher Maffeo, Himanshu Joshi, Aleksei Aksimentiev, Brice Ménard and Rebecca Schulman, 7 September 2022, Science Advances.
DOI: 10.1126/sciadv.abq4834
The study was funded by the National Science Foundation, the United States Department of Energy, and the Defense Advanced Research Projects Agency.