Unlike the rigid skeletons within our bodies, the skeletons within individual cells—cytoskeletons—are changeable, even fluid. And when these cytoskeletons reorganize themselves, they do more than support different cell shapes. They permit different functions.

Little wonder, then, that scientists who build artificial cells hope to create synthetic cytoskeletons that act like natural cytoskeletons. Synthetic cytoskeletons capable of supporting dynamic changes in cell shape and function could enable the development of novel drug delivery systems, diagnostic tools, and regenerative medicine applications.

Synthetic cytoskeletons have incorporated building blocks such as polymers, small molecules, carbon nanotubes, peptides, and DNA nanofilaments. Mostly DNA nanofilaments. Although they offer programmability, they can be hard to fine tune. To get around this difficulty, scientists based at UNC Chapel Hill led by Ronit Freeman, PhD, investigated the relatively unexplored possibilities offered by peptides. Specifically, the scientists engineered artificial cells using a programmable peptide–DNA nanotechnology approach.

Details recently appeared in Nature Chemistry, in an article titled, “Designer peptide–DNA cytoskeletons regulate the function of synthetic cells.” The article emphasizes that the bottom-up engineering of artificial cells requires a “reconfigurable cytoskeleton that can organize at distinct locations and dynamically modulate its structural and mechanical properties.” According to this article, the peptide–DNA approach represents progress toward the bottom-up assembly of dynamically reconfigurable artificial cells.

“Inspired by actin-binding proteins, we rationally designed peptide–DNA crosslinkers with varying sequence, length, valency, and geometry,” the article’s authors wrote. “We show here how filamentous peptides conjoined through DNA hybridization form tactoid-shaped bundles and networks with tunable aspect ratios and mechanics. When confined within cell-sized water-in-oil droplets, distinct structures are driven to spatially localize in the cortex or lumen, depending on the crosslinker attributes, and the extent of bundling tunes the mobility of intradroplet payloads from water-like to arrested. Finally, we show how different crosslinkers orchestrate changes in the cellular shape of lipid-encased droplets.”

Essentially, the Freeman Lab created cells with functional cytoskeletons that can change shape and react to their surroundings. And the scientists did so without using natural proteins. Instead, they used a new technology that directs peptides and repurposed genetic material to work together to form functional cytoskeletons that can change shape and react to their surroundings.

“DNA does not normally appear in a cytoskeleton,” Freeman noted. “We reprogrammed sequences of DNA so that it acts as an architectural material, binding the peptides together. Once this programmed material was placed in a droplet of water, the structures took shape.”

The ability to program DNA in this way means scientists can create cells to serve specific functions and even fine-tune a cell’s response to external stressors. While living cells are more complex than the synthetic ones created by the Freeman Lab, they are also more unpredictable and more susceptible to hostile environments, like severe temperatures.

“The synthetic cells were stable even at 122°F, opening up the possibility of manufacturing cells with extraordinary capabilities in environments normally unsuitable to human life,” Freeman said.

Instead of creating materials that are made to last, Freeman said their materials are made to task—perform a specific function and then modify themselves to serve a new function. Their application can be customized by adding different peptide or DNA designs to program cells in materials like fabrics or tissues. These new materials can integrate with other synthetic cell technologies, all with potential applications that could revolutionize fields like biotechnology and medicine.

“This research helps us understand what makes life,” Freeman declared. “This synthetic cell technology will not just enable us to reproduce what nature does, but also make materials that surpass biology.”

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