Imagine being able to control the delivery of drugs into your system on a cell-to-cell basis with never before seen precision. Now picture these drugs as programmable biological computers that can diffuse into specific cells at a set time to deliver therapeutics or detect any disease on demand.

We’re now a step closer to this premise thanks to scientists from the University of New South Wales who’ve worked out the optimal conditions to enable DNA robots to interact with cell membranes. They state their findings, published in Nucleic Acids Research, pave the way for mini biological computers capable of living in our bodies permanently.

Uniform layers of fat, such as cholesterol, make up our cell membranes separating the cell’s interior from the outside environment or extracellular space. The structure also contains proteins, forming pores that transport specific molecules into the cell interior.

Liposomes, hollow spheres made of the same types of fat, are widely used to mimic empty biological cells in the laboratory, being similar in nature and structure. As these vesicles are synthesized under controlled conditions, monitoring and recording their behavior is also easier.

The researchers used these artificial membranes to discern the best way to design and build DNA ‘nanostructures’ to manipulate biological bilayers in the body. The main problem was determining the best conditions to ensure their DNA computers stick to the fats or lipids making up liposome bilayers. Thus, the scientists alternated DNA machine design, liposome bilayer structure, and buffer composition to ensure this.

First, the team trialed differing DNA robots incorporating a cholesterol group to bind with the synthetic cell membrane. The DNA-based designs ranged from simple shapes to larger tiles folded multiple times using origami. The team positioned cholesterol at different locations around the folded DNA tiles to see which arrangement attached more firmly to the liposome layers. They found the optimal number of cholesterols is between 4 and 8, placed at the edges of the tile rather than the center to improve binding.

Once bound to the membrane, the DNA structures successfully modified the synthetic membranes’ shape, porosity, and reactivity. The lab theorizes this ability may create more applications, such as biosensing and signaled drug release.

The scientists then alternated the lipid species in the bilayer to test optimal conditions: this included increasing the cholesterol content, which raised DNA robot attachment by up to 20 percent. It was found that the pH of the buffer solution can also change the shape of the DNA robot, controlling its orientation and, in the future, how it interacts with cell membranes.

Lead author Dr. Matt Baker from UNSW’s School of Biotechnology and Biomolecular Sciences says, “Here we have built totally new DNA nanotechnology where we can punch holes in membranes, on demand, to be able to pass important signals across a membrane. This is ultimately the basis in life of how cells communicate with each other.” Adding that: “What’s better is because they are built from the bottom-up out of individual parts we design, we can easily bolt in and out different components to change the way they work”

The scientists now plan to use this technology to develop self-assembling synthetic retinas out of light-activated DNA nanostructures.

Medical photo created by kjpargeter – www.freepik.com

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