Numerous endeavors have sought to rebuild entire viral, bacterial, and eukaryotic genomes from scratch, exploring the seemingly limitless possibilities provided by such feats. Now, a team of scientists from UNC-Chapel Hill is exploring other cellular functions that can be rebuilt with a new first - an entirely artificial cytoskeleton. Detailed in a study published in Nature Chemistry, Ronit Freeman and her team have developed an innovative method of manipulating DNA and proteins, the fundamental building blocks of life, to create cells that mimic the structure and behavior of cells found in the human body. This development carries significant implications for the advancement of regenerative medicine, drug delivery systems, and diagnostic tools.

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“With this discovery, we can think of engineering fabrics or tissues that can be sensitive to changes in their environment and behave in dynamic ways,” explains Freeman, whose laboratory is situated in the Applied Physical Sciences Department of the UNC College of Arts and Sciences.

The cells and tissues in our bodies are primarily composed of proteins, which assemble to carry out various functions and construct cellular structures. Proteins are crucial for forming the cytoskeleton, the framework of a cell. It is the cytoskeleton that enables cells to maintain flexibility, adapting both their shape and behavior in response to their surroundings – without it, cells would be unable to function properly. 

Freeman's lab managed to construct cells with functional cytoskeletons capable of changing shape and responding to their environment. Instead of relying on natural proteins, they utilized programmable peptide-DNA technology to direct peptides (the building blocks of proteins) and repurposed genetic material to form a synthetic cytoskeleton.

“DNA does not normally appear in a cytoskeleton,” Freeman explains. “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.”

This type of DNA programming allows scientists to create cells tailored to specific functions and even adjust a cell's response to external stimuli. Although the synthetic cells are less complex than their living counterparts, they are also more predictable and less vulnerable to harsh environmental conditions, such as extreme temperatures.

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

Unlike conventional materials designed for longevity, Freeman emphasizes that their materials are task-specific — designed to perform a particular function and then adapt to serve a new one. By incorporating different peptide or DNA designs, scientists can customize the application of these cells in materials such as fabrics or tissues. These innovative materials can be integrated with other synthetic cell technologies, promising revolutionary applications in biotechnology and medicine.

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