UC Moves a Step Closer to Engineering Cells Via Foam

One University of Cincinnati College of Engineering and Applied Science (CEAS) researcher is bridging the gap between the conception and application of engineering life in vitro. In vitro experiments in biology are conducted using parts of an organism that have been isolated from their usual biological surroundings in order to permit a more detailed or more convenient analysis than can be done with whole organisms.

Hyo-Jick Choi, CEAS research assistant professor, and his colleagues have recently discovered an unlikely candidate for engineering and supporting life—

ranaspumin-2 foam

, the foam nests of frogs. Their ground-breaking findings, detailed in the article, “pH Stability and Comparative Evaluation of Ranaspumin-2 Foam for Application in Biochemical Reactors,” were featured on the February cover of "Nanotechnology" journal.

Ranaspumin-2 foam is one of six proteins used by the tungara frog to form protein foam nests in which it deposits its eggs. Choi, along with his student Charles Ebersbacher and colleagues from the University of Alberta in Canada and Kyung Hee University in South Korea, have carried out research to evaluate ranaspumin-2 foam as a potential biochemical reactor (a manufactured or engineered device or system that supports a biologically active environment, allowing life to be engineered and sustained). They found that the foam maintains strong surfactant activity (which reduces the work needed to create the foam) above pH 3.0 and exhibits desired stability for sustaining engineered life. Combined, these factors show a potential for application to various applications when dealing with the production of complex molecules within living organisms or cells. The researchers also proved that ranaspumin-2 shows excellent compatibility with the behaviors of various model cellular systems such as liposomes and inactivated H1N1 influenza virus, and bacterial E. coli cells.

This research originated in Choi’s graduate study at the University of California, Los Angeles (UCLA), as he realized that engineering complex biochemical cascades in vitro had been limited by the difficulty of subcellular compartmentalization and the locally high concentration of biochemicals. Choi teamed up with Carlo Montemagno, former CEAS dean and also a former UCLA faculty member, to address the issue. Together, they were the first to propose the possibility of using foams as a bioreactor platform.

Choi explains, “This research is expected to contribute to the development of long-term stable biocompatible foam formulations for in vitro foam-based bioreactors. That is, the ideas and materials obtained from nature can be used to reconstruct complicated cellular processes in foam. Living organisms can maintain their life processes in the aqueous channels of foam. Thus, the meaning of our research is that it brought us one step closer to the reproduction of in vitro engineering of life in the bubble architecture.”

Once again, UC is leading the way in this research. UC’s uniqueness spurs from researchers’ rheological (the study of the flow of matter, primarily in the liquid state, under conditions in which they respond with plastic flow instead of deforming elastically in response to an applied force) techniques, cellular/molecular biology techniques, and skills of artificial cell production, which are all crucial factors in replicating

in vitro

cellular process in foam. Choi says, “I do not have any hesitation in saying that our team at UC has been taking the lead in the foam technology from the creation of the research area to the advancement of its application.”

Choi’s research has centered on the development of new nanobiological systems and their applications in drug delivery as well as the fabrication of engineering devices with life-like functionality. He is currently focusing on the development of optimal foam formulations that are biocompatible and stable for extended periods of time at high temperatures, and also the application of more complicated biochemical reactions in foam. Choi’s feature article in "Nanotechnology" describes a new foam platform that he and his team have designed and are currently testing.

Foam has major advantages such as an easy, low cost fabrication process that produces micro and nano-fluidic channels as well as locally high concentration of biochemicals. There is a strong need to validate the potential value of this approach, and more research efforts are being made to develop long-term stable, biocompatible foams. Once the physicochemical and biochemical stability issues of foam are solved, Choi predicts that bubble architectures will provide alternative methods to conventional silicon-based devices and to widely-used bioreactors.

Choi further explains, “The ultimate goal of our efforts is to use the aqueous channels of foam as a low cost and convenient way to create a sub-cellular structure, providing a platform for integrating cellular metabolism and engineering of biofunctional systems within the bubble architecture. Cells can be cultured and cellular metabolisms can be replicated in the foam, i.e. out of traditional biochemical reactors.

For example, biological organisms such as viruses, yeasts, bacterial/mammalian cells, and artificial organelles can easily be housed and multiply within aqueous channels of foam. This technology can be used to produce biological products such as proteins, vaccines, peptides, and pharmaceutical molecules as well as to construct biocomputers (the use of systems comprised of biologically derived molecules, like DNA and proteins, to perform computational calculations involving storing, retrieving, and processing data) through inter/intra-cellular communications in the foam.”

Choi received his master's of science in bioengineering and biomedical engineering from UCLA in 2006. He went on to earn his doctorate in the same field from UC in 2007. From 2009 to 2010, Choi was a post-doctoral fellow at the Georgia Institute of Technology. He came back to UC to serve as a research assistant professor in 2010. To date, he considers his most significant research achievement to be the reconstruction of a mitochondrial adenosine triphosphate (ATP) synthesis process from the bacteriorhodopsin/ATP synthase reconstituted polymer vesicles.

Choi has always had a fascination with living organisms and their ability to carry out certain life processes with optimal functionality. He describes, “As living organisms represent a good model for engineers to learn from, I had a belief that many technical problems could be solved if we apply the ideas of nature or utilizing natural materials to control life processes. A crucial step for the construction of innovative systems is to understand how the natural components function, how to functionalize materials, and where to apply it. Throughout my academic and research career, I kept this in my mind, which provided motivation to study diverse fields such as materials science and engineering, biomedical engineering, chemical engineering, and environmental engineering.”

Currently, the methods, approaches, and foam formulations of bubble technology that Choi and Montemagno invented are in the process of being patented. Choi and his colleagues’ recent revelations will undoubtedly lead to more patents and more breakthroughs. Choi reflects, “We owe our research performance to UC’s outstanding environment, producing highly skillful researchers and encouraging interdisciplinary collaboration. I was lucky to have found excellent undergraduate students through UC’s

cooperative education

(co-op) program. This research project would have been impossible without the help of Charles Ebersbacher, my undergraduate student in the biomedical engineering program.”

Inspired by the skills and talents of his undergraduate students, Choi plans to continue his research looking for new nanobiological systems in the future as well as serving as an advisor to students.