Bacteria have plenty of superpowers, and one of them is their building skills. Proteins inside the bacteria can assemble themselves into intricate, repeated structures that can look like honeycombs.
Inside the bacteria, these self-assembling structures can package up enzymes or box away potentially toxic compounds. But when, as a postdoctoral researcher, Carolyn Mills took these same building blocks out of their bacterial environment and set them loose in a test tube, they started to form incredible new structures on their own, from long fibers to enormous discs made of hexagons.
“We didn’t believe what we were seeing at first,” said Mills, now an assistant professor of bioengineering at UC Santa Barbara. “But once we realized what was happening, it was so exciting.”
“Then, I started wondering — could this be useful?”
Now, with a new grant from the U.S. Department of Energy (DOE), she’ll start to uncover some answers to that question — answers that could point to an entirely new way of making materials. By harnessing nature’s ability to build complex structures like these, what she learns could potentially reduce their dependence on energy-intensive processes commonly found in manufacturing.
Mills will receive $875,000 over five years for her project, “Design Rules for Autonomous Propagation of Order in Hierarchical Biological Block Copolymers,” through the DOE’s 2026 Early Career Research Program.
The program, which aims to support exceptional researchers pursuing rigorous work in critical areas of science and technology, awarded $96 million to 67 researchers across the country.
“Groundbreaking science begins with empowering extraordinary people,” DOE Under Secretary for Science Darío Gil said in a press release. “These 67 early career researchers represent the very best of American ingenuity.
DOE is proud to invest in their vision as they push the boundaries of knowledge and cement U.S. leadership in the technologies that will define our century.”
Inspired by Nature
“A lot of really inspiring materials that we see in nature have really cool properties,” Mills said. Take spider silk, with its high tensile strength, or nacre, the iridescent coating on some sea shells, known for its resilience.
It’s the organization of these natural materials that makes them unique, Mills said — and of particular interest for bioengineering. Nacre, for example, is made of discs of a mineral called aragonite, stacked in intricate layers that confer strength. “It’s less about the individual components, and more that they’re organized in this really exquisite way.”
The organization of self-assembling bacterial structures is what fascinates her, too. The hexagonal protein tiles that she is studying maintain their organization across multiple scales, making first nanometer-scale structures, and building them into millimeter-scale honeycombs with the same pattern.
What Mills hopes to learn through her project is how that organization persists as the structures grow, and whether the same principles could be used to design materials that assemble themselves in larger, precisely ordered forms.
Saving Energy with Order
Bioengineers understand that this organization is critical, but Mills said, “it does fly in the face of a lot of the ways we think about proteins.”
Proteins, Mills’ biomolecules of choice, are known for their sequences. In fact, the 2024 Nobel Prize in Chemistry went to research looking at how a protein’s sequence of amino acids gives rise to its folding structure.
With this project, Mills wants to look at proteins and their behavior at a bigger scale.
“I’m trying to understand ways that we can achieve the same type of hierarchical order in synthetic materials,” she said, including learning more about the natural “machinery” that might help bacteria build these structures.
Beyond creating fascinating structures, this self-assembling property could inspire new, more efficient ways of building. “Even normal materials that we use in everyday life often have to undergo a lot of processing to define their final features,” Mills said, “and that processing can be very energy intensive.”
Many high-performance synthetic materials being designed today have a similar hierarchical structure as these self-assembling natural structures, starting the pattern of building at the molecular level and then repeating it.
If self-assembling proteins could be part of the building process, she said, materials could be made more efficiently, and even repair themselves.
A Structure in Hand
To learn how proteins assemble themselves into larger structures, Mills and her colleagues are modifying their surfaces with molecular components that act like glue. By observing how these additions change how proteins connect and organize, she hopes to identify the principles that govern how these orderly structures form and grow.
One of the highlights: the structures they’re building are big enough to see. “What was really cool when I started working with some of these ideas is seeing the actual change, or being able to hold something in my hand,” Mills said. “When these proteins begin their assembly behavior, all of a sudden, you’re seeing these crystal-like structures in solution. I think, Oh my gosh, it’s real.”
Mills is looking forward to beginning to turn self-assembling proteins into new materials, using nature as a guide.
“I like to think about how nature accomplishes things,” she said. “We can't always do it the same way, but we can take inspiration from nature, and develop a good understanding of how nature builds larger structures that are greater than the sum of their parts.”
Photo Caption: Protein researchers, assemble: assistant professor of bioengineering Carolyn Mills (second from left) and PhD students (from left) Janelle Arnold, Natasha Jones, and Juyeon Ha. Photo credit: Lilli Walker
