A multidisciplinary approach to a biomolecular problem

Living organisms arrange proteins and DNA into intricate systems that accomplish wide-ranging sensing, information-processing, mechanical, and chemical functions. These naturally occurring biological designs are difficult for engineers to match in complexity and efficiency. If they could, these biomolecular systems could have broad applicability and functionality in materials, computing, and other applications. “Unfortunately,” says Dr. Amy Keating, “current methods are slow and costly. We need to learn how to synthesize giant user-defined biomolecular systems with the complexity of integrated circuit patterns.”

Combining her expertise in biological engineering with that of her collaborator, electrical engineer Dr. Karl Berggren, the pair conceived a means to develop methods and tools to construct complex, nano-scale assemblies of biological molecules on surfaces. The project leverages each of the labs’ capabilities; applying the two disciplines to a single objective is novel and promises to take their work farther than any previous efforts. The chief responsibility of Dr. Keating’s lab is to design custom protein molecules while Dr. Berggren’s lab will be focused on making patterned substrates with specific features through electron-beam lithography—together, they seek to construct a unique nano-bio interface design platform.

Protein engineering enables bottom-up design, while lithography provides top-down templating; we believe the two can be combined to create new types of materials,” says Dr. Keating. “Such a framework could power discovery and engineering in the life, materials, and information-processing sciences, and enable new types of nano-manufacturing.”

Taking a broad, long-term view turns off traditional funding sources

The interdisciplinary nature of this approach (combining electrical engineering, materials science, and protein biology) is necessary, but is difficult to accommodate in traditional funding mechanisms. The pair previously obtained some support for this type of work from a major global chemical and life sciences company, but there was pressure to steer the work towards near-term applications. “That was in conflict with our goals of creating new basic capabilities to support a broad range of as-yet not imagined applications,” says Dr. Keating.

Our goals are to make new parts, develop new methods, optimize processes, explore opportunities, and identify limitations,” Dr. Berggren adds. “These goals are too basic for most industry funding.”

Building on early successes, hopeful for lasting impact

The pair plan to introduce additional complexity into their systems by designing a broader range of structures, diversifying their toolkit of surface attachment strategies, and aligning protein structures to more complex surface patterns. Ultimately, the goal of their research is to engineer solutions such that the surface can effectively direct the organization of the proteins into larger, programmed complexes and assemblies.

A lot more than just scratching the surface

Over the course of the three-year grant period, the team has been exploring how proteins (designed in the Keating lab) and surfaces (prepared in the Berggren lab) can be coupled such that the proteins are positioned in a desired way on the surfaces. As the project progressed, with the two groups working closely to develop and explore a wide range of ideas, the protein assembly work had the most significant early advances, according to Dr. Berggren.

“One of our joint post-docs discovered it was possible to assemble nanoscale triangles by chemically attaching component blocks of proteins to each other,” he says. “By combining them in the right order, innate affinities within the blocks act like a magnet and attract, creating dimers that naturally form a stable triangular shape.” Having achieved this, the team is now working on a paper that will show how the distribution of gold dots on a microsurface is copied from the spacing in the triangle structure—proving that the surface structures have an ordered payload.

“One of the most rewarding things about the Bose Fellows imprimatur is that our two postdocs were both able to find excellent faculty positions at other institutions,” says Dr. Berggren. “I believe their ability to work on ‘out there’ ideas impressed the hiring committees. On a personal level, the chance to work across disciplines has gotten me more interested in exploring what kinds of interactions I might be able to pursue in biology. This experience has definitely broadened my group, which is very fulfilling.”