Bioengineers and physicists at Harvard University and the California Institute of Technology have used the heart cells of a rat and a silicone scaffolding to build an artificial jellyfish whose movements mimic the rhythmic pumping of the heart muscle and could help drug makers improve cardiac function.
Until now, researchers have been able to measure how some heart drugs help muscles contract, but they've not been able to fully understand how they might work on the pumping action, said Kevin Kit Parker, a professor of bioengineering and applied physics at Harvard's School of Engineering and Applied Sciences, who got the idea to create a synthetic jellyfish after visiting the New England Aquarium in Boston.
The visit got Parker thinking about how jellyfish use their muscles to pump their way through the water and how this movement might relate to the pumping of blood in the human heart.
'I remember looking at the jellyfish, thinking, "I can build that".' — Kevin Kit Parker, Harvard University bioengineer
He was interested in understanding the mechanics of the heart's muscular pump at the cellular level and how that relates to disease. Parker had a hunch that if he identified some similarities that human muscular pumps share with muscular pumps in other species, he might have a better understanding of what can impede their function.
"I remember looking at the jellyfish, thinking, 'I can build that,'" said Parker in an interview with CBCNews.ca. "And that kind of dovetailed with what I was trying to do, and that's understanding what the fundamental rules are for muscular pumps across nature."
As he sees it, "if you understand what the fundamental rules are, when the rules get broken, that's your disease, and sometimes, just really understanding what the disease is is the first step in curing it."
Jellyfish propelled by pacemaker
As head of Harvard's interdisciplinary disease biophysics group, Parker already had experience building tissues from cells for the purpose of testing new drugs and was confident that with some help from John Dabiri of Caltech, an expert in fluid dynamics and biological propulsion, he could build something that would mimic the jellyfish's movement.
It took the two of them, along with Dabiri's PhD student Janna Nawroth, four years to create their "medusoid," which looks like a jellyfish, swims like a jellyfish but whose motion is controlled by the cells of a rat heart mounted on a body made of a silicone polymer, the same material that is used to make breast implants.
The researchers' creation, dubbed 'medusoid' after Medusa, the name sometimes given to jellyfish because their tentacles resemble the snakes on the head of the Greek mythical creature, is described in a paper published in the July 22 issue of Nature Biotechnology.
When Parker, Dabiri and their colleagues set about studying what drives a jellyfish's heart-like pumping motion, they found it has a pacemaker, like human and animal hearts do, that sends electrical signals to muscles causing them to contract rhythmically in a pumping motion.
That similarity enabled the researchers to use cells from the heart of a rat to construct their synthetic jellyfish, which they modelled after the Aurelia aurita species of jellyfish, known as the moon jellyfish.
Motor protein structure similar
Even though rat heart cells and jellyfish cells are shaped differently, the proteins that drive their motor function are arranged in remarkably similar networks, Parker said.
That made it easier to coax the rat cells to behave like jellyfish cells.
"When we built the jellyfish, all we had to do was get the rat heart cells to rebuild their protein motor networks in the same orientation and the same architecture and same alignment as the jellyfish," Parker said.
To do that, the researchers built a type of biochemical scaffolding that they stamped onto a thin, flexible silicone film and let the cells assemble themselves on it.
But unlike the wood, steel and other inanimate materials that civil engineers work with, the cells Parker and Dabiri were manipulating had a will of their own, and the bioengineers had to first learn how to control them in order to get them to arrange themselves in the right pattern.
"We can control the surface chemistry on the polymer thin film, and when the cells came down there, it's just like when you're driving and you're reading street signs," Parker said.
"Basically, the cells saw all these directions. We knew how they were going to behave when they saw them, so we put all these geometric cues in the surface chemistry in order to guide their behaviour."
'Morphologically, this thing is a jellyfish; functionally, this thing is a jellyfish; but genetically, it's still a rat.' — Kevin Kit Parker, Harvard University bioengineer
It took a few tries to get just the right blend of a rat's heart chemistry and a jellyfish's muscle geometry.
"The environment had to be a little bit like a rat so the rat cells felt comfortable, but it had to be a little bit like a jellyfish, so they would function like a jellyfish," Parker said. "We had to go through several different builds in order to strike a balance between the microenvironment of the rat heart and the microenvironment of the jellyfish musculature."
One unique aspect of the study is the method the scientists used to check their work. To see how well the protein networks in their artificial jellyfish aligned with the ones in the real organism, Parker and his colleagues used the same mathematical algorithm police use when analyzing fingerprints.
Parker said that while this type of quality control and performance testing is nothing new in the manufacturing industry, it hasn't really been applied as rigorously in the area of tissue engineering.
Replicated complex feeding motion
Part of that performance testing was ensuring that the medusoid not only moved like a real jellyfish but did so at the same speed and was also able create the same kind of complex currents and vortices in water that jellyfish do when they feed.
A jellyfish's mouth is up inside its bell-shaped body so the only way, it can feed itself is to spin a vortex off the tip of what are known as the lappets, the crinkly sensory structures that rim the edge of the bell, and that throws the food up toward the mouth, Parker says.
Similar vortices occur in the human heart during systole, or contraction, and can indicate whether the heart is functioning properly. So, it was a big deal when the scientists were able to verify that their synthetic jellyfish was creating the same feeding currents as a real jellyfish.
"Then we knew it wasn't just about this thing flopping around in the water," he said.
Once the medusoid was built, Parker and his colleagues placed it in nutrient-rich, ocean-like salt water and used electrical currents to test its motion in a controlled manner, but the synthetic jellyfish was also able to swim on its own.
"A lot of times as soon as we released these things from the scaffold that held it in place while the cells were aligning, they would just start to swim away, and that's because they had their own autonomous feeding," Parker said.
Medusoid will help test potential new drugs
Now that they have standardized a way to build medusoids, the researchers can use them to do some early-stage testing of the efficacy of potential new heart drugs that are meant to improve the pumping function of the heart.
The next goal will be to replace the rat cells with human heart cells.
But that still leaves the question whether the current incarnation of the medusoid is more like a jellyfish, thought to be one of the earliest multi-organ animals, dating back several hundred million years, or a rat, a more recent arrival on Earth.
"Morphologically, this thing is a jellyfish; functionally, this thing is a jellyfish; but genetically, it's still a rat," said Parker.
The dilemma over how to classify the medusoid raises some tricky philosophical questions about how we identify a species, he adds.
"Nowadays, with genetic sequencing, we identify people and species by their genome, but the custom in naming marine life forms has been to identify them based on their body shape, so it's kind of like, which lens do you view this through?"
"Should we change the fundamental way by which we identify different species now that we have the technology to sequence their genome?"