By studying the behavior of living cells and combining them with synthetic tissue, researchers are creating “biological machines” to deliver drugs more effectively, function as internal diagnostic tools or serve as contaminant sensors in the field.
This work is facilitated by a multi-institution effort known as the Emergent Behaviors of Integrated Cellular Systems, which recently received $25 million in National Science Foundation renewal funding for the next five years to build living, multicellular machines to solve environmental, health and security problems.
The EBICS project is unique in that both the funding and management are shared equally by the primary participants, which include the University of Illinois at Urbana-Champaign, the Georgia Institute of Technology and lead institution, the Massachusetts Institute of Technology. Eight other institutions also provide research assistance.
According to Rashid Bashir, EBICS co-principal investigator and head of the department of bioengineering at Illinois, the goal of the project is to build non-natural functions with cells. “Take vascular disease, for example," Bashir said. "One could approach the problem from the standpoint of, ‘What if we could take passive vascular cells and combine them with cardiac muscle cells to create vascular tissue that could pump?’ Such devices would allow patients’ own bodies to become part of the solution.” The group’s efforts aren’t limited to improving human health. “We’re also interested in building living machines that can do things like sense toxins in water and potentially neutralize them,” he said.
In the first phase of the project, the researchers examined the behaviors of muscle, neuronal and vascular cells. Although much is known about how these cells function, little was known about integrating them.
“We needed to learn how to grow diverse cells together, as each has its own ideal growing conditions,” Bashir said. “We also needed to learn how to get them to communicate with each other.”
Developing so-called biobots takes a wide range of expertise. Bashir is joined on the U. of I. EBICS team by professors Martha Gillette, of cell and developmental biology, Hyunjoon Kong, of chemical and biomolecular engineering, Gabriel Popescu, of electrical and computer engineering, and Taher Saif, of mechanical science and engineering.
Gillette’s group develops neuronal circuits to provide sensing and processing. Kong develops new scaffolds and biomaterials to “house” the cells and the machines. And Popescu develops new imaging techniques to visualize and study the emergent behavior of living cells over time.
Saif’s group developed one- and two-dimensional swimming bots whose locomotion tissue is made from soft polymers and 10-micron-thick films. These millimeter-scale “swimmers” can propel themselves in one direction using the force generated by heart muscle cells. According to Saif, this research could pave the way for internal diagnostics that are more accurate than poking or prodding, or they can be developed to deliver drugs to treat disease.
For another biobot, the researchers randomly placed rat heart muscle cells on a layer of soft plastic hydrogel that they designed and printed with a 3-D printer. The natural contracting and relaxing of the cells allowed the bot to pull itself along or “walk” in culture medium.
Another “walking” device relies on skeletal muscle cells. It responds and moves on command to electric fields. Most recently, the team has been working with muscle cells that can be controlled remotely by blue light and could be the key to developing new remotely controlled tissues and systems.
Another major component of the center is the ethical context of the ongoing and future research. Former U. of I. professor of education Lizanne DeStefano, who currently heads Georgia Tech’s Center for Education Integrating Science, Mathematics and Computing, coordinated the team that is developing ethics modules to ensure faculty members and students are always cognizant of the ethical implications of their work.