A multicenter, NSF-funded research team is building machines with new functionalities out of living cells.April 17, 2017
Blood vessels don’t naturally pump blood, but imagine ones that could. A blood vessel that supplies the heart could be engineered to sense rising pressure from a blood clot in a clogged artery, and start pumping to disperse the clot. Or imagine a swimming, sperm-like robot powered by muscle cells that could swim in a patient’s bloodstream, seek out hidden tumors inside her body and deliver targeted doses of life-saving drugs.
The first such biological machines are just now being built. Funded by the National Science Foundation, a consortium of researchers at major engineering schools have developed a handful of biological machines that can sense input, move, or both.
So far their devices are rudimentary, but the scientists are aiming for cellular machines that not only behave as simplified organs, but also improve upon their design.
Unlike today’s tissue-engineered organ replacements, which seek to replace or repair damaged organs, these new machines harness cells that like muscle and nerve cells that make up tissue, and put them together in ways nature never has. The goal is to build living, multicellular machines that sense, move and solve real-world health problems.
“When we put these building blocks together, we can capitalize on their individual functionalities and make something new to serve whatever purpose we want,” said Caroline Cvetkovic, a postdoctoral bioengineer from the University of Illinois, Urbana-Champaign, one of the 10 research institutions on the NSF project, which is called Emergent Behaviors of Integrated Cellular Systems (EBICS).
The microswimmer, a cell-based robot built by bioengineer Taher Saif and colleagues, consists of beating heart cells arranged on a flexible microfilament string, and it propels by flexing and extending, much like the tale of sperm. Image: Brian Williams, University of Illinois, Urbana-Champaign.
Propelling the Biobots
These new biological machine-building capabilities build on recent advances in genetic engineering, bioinformatics, and stem cell engineering. Scientists can now genetically program cells to express proteins that give cells prescribed functions, such as the ability to sense and respond to light or pressure.
One of the first and most rudimentary biobots is the microswimmer, which is part animal, part machine and most closely resembles a sperm.
The microswimmer consists of a flexible microfilament string about the thickness of a human hair, with a bundle of cardiomyocytes—heart muscle cells—clustered at one end. As the cardiomyocytes beat in synchrony, they bend the string and propel the biobot forward.
“We used cardiomyocytes because can they self-organize, synchronize their beating and mimic a swimmer,” said Taher Saif, the designer of the bot and bioengineer at University of Illinois at Urbana-Champaign. One day this bot may be programmed to sense chemical signals emitted from cancer cells, seek them out, and deliver tumor-destroying chemicals, he said.
Another EBICS group has developed a biobot that walks. Inspired by the structure of human joints, this walker has two short, stubby legs connected by a bridge. The skeleton is constructed from a soft Jell-O-like 3D-printed skeleton called a hydrogel, and it’s surrounded by a band of skeletal muscle. Just as a muscle in the body contracts and moves a bone, these muscles contract to move the hydrogel skeleton.
In building the walker, Rashid Bashir’s team at the University of Illinois, Urbana-Champaign used skeletal muscle cells instead of heart cells. That’s because heart cells beat on their own, whereas skeletal muscle needs a stimulus to contract, which allows the engineer to actuate them on command.
Skeletal muscle contracts naturally in response to electrical current, and at first Bashir and his colleagues used electricity as the stimulus. But their latest biobot responds to light. The group genetically engineered the cells to produce a protein called channel rhodopsin, a sensory photorecepter that enables the muscle to contract in response to blue light. This provides an easy on-off switch to activate the muscle, spurring the bot to move its legs and walk.
Why use biological materials to construct machines at all, as opposed to building machines with more traditional materials like metal, ceramic and plastic? There are many advantages, Saif said. To start, you don’t need a motor. The heart cells that power the swimmer, for example, beat in synchrony and generate enough power to actuate the device.
In addition, individual cells self-organize and condense into tissues without much prompting from a scientist, a phenomenon called emergence. To make muscle for the walker, Bashir’s team simply combined the 3D-printed skeleton, 1.5 million lab-grown muscle stem cells, and extracellular matrix proteins like collagen and fibrin in a small mold. Within a day, the muscle stem cells had linked to the proteins, condensed and aligned themselves into a band of solid muscle the length of a staple that could move the skeleton as a human muscle moves bone.
Birds flying in a flock, fish swimming in a school and even civilizations organizing themselves around major riverways like the Nile or Ganges are other examples of emergence. Cells, too, organize themselves. During development, they sense, and process, act on each other to form tissues and organ systems.
As biologists understand those rules better, bioengineers will be capable of reverse-engineering development to better program cells to self-assemble to create biological machines. In the case of Saif’s microswimmer, “We didn’t do much at all; we just put the cells in randomly,” he explained. “They had the power within themselves and were cross-talking to one another.”
Plans for future bots will include different cell types and many more functionalities. Bashir’s team would like the walker to employ nerve cells due to their built-in ability to sense and respond to chemical cues. Also in the works are artificial vascular systems that will be able to supply the interior of biological machines with oxygen and nutrients. In the future, biological machines could also repair themselves, as many tissues do.
For now, the next milestone will be a biological machine containing a functional neuromuscular junction. Said Saif: “This will be the first biological machine with multiple cell types and potential intelligence.”
Credit: Artist's depiction of biobot (lead image) courtesy of Rashid Bashir, University of Illinois, Urbana-Champaign.
Monique Brouillette is a science and technology writer in Cambridge, Massachusetts.