Playing molecular Legos with viruses

Researchers at UC Berkeley have turned a benign virus into a tool that assembles structures similar to collagen--a process that could be used to create complex tissues such as corneas and bones.

It may be benign, but researchers have turned the virus M13 into a sophisticated engineering tool that could lead to the manufacturing of materials with biomedical properties that can be fine-tuned, such as bone, skin, and corneas.

The virus helped the researchers engineer a material that could eventually be used to create complex tissues such as corneas and bones. Woo-Jae Chung/UC Berkeley

"We took our inspiration from nature," said Seung-Wuk Lee, an associate professor of bioengineering at UC Berkeley who describes the team's self-templating material assembly process in the journal Nature. "Nature has a unique ability to create functional materials from very basic building blocks. We found a way to mimic [this]."

Lee points to the protein collagen as the basic building block for functional biomaterials such as corneas, skin, teeth, and bone. The team decided to investigate exactly which factors influence collagen's formation of hierarchical structures with diverse functions.

One example Lee likes to use is the blue-faced Mandrill, whose color does not come from pigment but rather a specific scattering of light that is formed when thin fibers of collagen are twisted and layered in its skin.

But because it's tricky to fine-tune collagen's physical and chemical structures, the researchers had to come up with a model system so they could investigate further.

They chose to use a soup of saline solution with varying concentrations of the bacteria-attacking virus called M13 bacteriophage because it is harmless to humans and, with its long shape and a helical groove on its surface, quite closely resembles collagen fibers.

The scientists then dipped a sheet of glass into the bath of M13 and pulled it out at slow, precise speeds. As the sheet emerges, a fresh film of viruses is attached. (By pulling between 10 to 100 micrometers per minute, each sheet took anywhere from 1 to 10 hours.)

It was the adjustment of speed and concentration of M13 that allowed the researchers to fine-tune the liquid's viscosity, surface tension, and evaporation rate, which in return changed the patterns formed by the virus. They were able to create three distinct film patterns in this way.

The team then engineered the virus to express specific peptides, thereby influencing the growth of hard and soft tissue, and used the resulting films as tissue-guiding templates to help form a composite similar to tooth enamel that could conceivably be used as regenerative tissue.

Lee says that their technique's simplicity is key; by setting very specific parameters, they just let self-assembly slowly take place: "We let this run overnight, and by the next morning there were trillions of viral filaments arranged in patterns on our substrate."

One of their key findings, Lee said, is that "we have started to understand nature's approach to creating such complex structures, and we have developed an easy way to mimic and even extend it."

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