Engineers at UCLA have discovered a way to alter cell metabolism that allows cells to artificially communicate with each other, according to a study published in the journal Proceedings of the National Academy of Sciences. If cells can communicate in this fashion, say researchers, coordinated cellular action is possible. Cells acting in unison could, for example, be directed to create greater quantities of a chemical compound that would later be used in the manufacture of chemicals or pharmaceuticals.
“Concerted biological behavior is certainly more easily achievable if cells can communicate,� said James Liao, co-author of the study and professor of chemical engineering at the UCLA Henry Samueli School of Engineering and Applied Science. “It’s an important step toward a more biologically based means of producing chemical compounds with desired properties.�
The study describes the construction of a gene-metabolic circuit that mimics a natural mechanism cells use to “talk� to each other. In the UCLA experiments, cells of the bacteria Escherichia coli sent out signals by secreting acetate, and reacted in concert once the acetate reached a certain threshold concentration.
Liao’s research is part of a field known as metabolic engineering, which involves altering cell metabolism, including the biochemical reactions and all the control circuits associated with it, so the cell can perform non-native functions such as producing a specific chemical, behaving as a sensor or even acting as a diagnostic tool.
Artificial gene circuits that resemble the natural circuitry in the cell have already been designed by researchers, and have led to bacterial strains that exhibit programmed behavior. But these artificially created networks are isolated from cellular metabolism and are designed to function without intercellular communication. According to Liao’s study, much more complex designer biosystems can be possible if cells are engineered to communicate with each other.
“Synchronized cellular behavior could lead to the manufacture of chemicals using renewable resources and environmentally friendly processes,� Liao said. “Most of our chemicals today come from petroleum. In the next few decades the goal is to replace petroleum-based chemicals with biologically based chemicals.�
Cargill-Dow, Dupont and other large chemical companies already are developing and producing key chemicals using metabolic engineering, Liao said.
Liao has created an artificial mechanism so that the cells used for his study will secrete low levels of acetate all the time, turning each cell into an artificial sensor by alerting nearby cells of its presence.
“We are mimicking the natural mechanism that cells use to talk to each other in nature,� Liao said. “For example, an individual pathogen secretes a chemical, much like an animal secretes pheromones, and when a pathogen senses a certain level of chemicals from similar pathogens, it reacts by attacking the host. Like individual soldiers who wait for reinforcements to arrive, so too do pathogens.�
Altering cell metabolism is a biologically based approach that can be used to create chemical compounds that are later used in the manufacture of plastics or pharmaceuticals. For instance, lactic acid and other monomers for plastics could be produced more naturally through metabolic engineering. Constructing chemical compounds through the use of bacterial cells instead of molecules from non-renewable fossil fuels like petroleum is more environmentally friendly and cost-effective.
UCLA has been involved in metabolic engineering for many years. In 2000 Liao published a paper that described the creation of a control circuit to direct the metabolic flow in the cell. The current study evolved from that earlier work.
“The earlier approach does not allow cells to communicate with each other,� Liao said. “In order for the cell to produce the desired chemicals in an effective way, cells must coordinate with each other to produce simultaneously a large quantity of a compound.�
The UCLA research could also lead to other applications.
“Cell-to-cell communication makes possible the design of intelligent bio-circuits,� Liao said. “Bio-circuits will lead to specialized computational functions and in the long term it could be used for building intelligent prosthetics and medicines.�
The research is supported by a National Science Foundation grant and the UCLA Center for Cell Mimetic Space Exploration. Other contributors to the study are lead author Thomas Bulter, Sun-Gu Lee, Wilson WaiChun Wong, Eileen Fung and Michael R. Connor.