A still of the artificial jellyfish “swimming” in container of ocean-like salt water. Note: the color and contrast of the artificial jellyfish has been digitally enhanced to make it easier to view. Image: Harvard University and Caltech
Using recent advances in marine biomechanics, materials science,
and tissue engineering, a team of researchers at Harvard University and the
California Institute of Technology (Caltech) have turned inanimate silicone and
living cardiac muscle cells into a freely swimming “jellyfish.”
The finding serves as a proof of concept for reverse engineering
a variety of muscular organs and simple life forms. It also suggests a broader
definition of what counts as synthetic life in an emerging field that has
primarily focused on replicating life’s building blocks.
The researchers’ method for building the tissue-engineered
jellyfish, dubbed “Medusoid,” was published in Nature Biotechnology.
An expert in cell- and tissue-powered actuators, coauthor Kevin
Kit Parker has previously demonstrated bioengineered constructs that can grip,
pump, and even walk. The inspiration to raise the bar and mimic a jellyfish
came out of his own frustration with the state of the cardiac field.
Similar to the way a human heart moves blood throughout the
body, jellyfish propel themselves through the water by pumping. In figuring out
how to take apart and then rebuild the primary motor function of a jellyfish,
the aim was to gain new insights into how such pumps really worked.
“It occurred to me in 2007 that we might have failed to
understand the fundamental laws of muscular pumps,” says Parker, Tarr Family
Professor of Bioengineering and Applied Physics at the Harvard School of
Engineering and Applied Sciences (SEAS) and a Core Faculty Member at the Wyss
Institute for Biologically Inspired Engineering at Harvard. “I started looking
at marine organisms that pump to survive. Then I saw a jellyfish at the New
England Aquarium and I immediately noted both similarities and differences
between how the jellyfish and the human heart pump.”
To build the Medusoid, Parker collaborated with Janna Nawroth, a
doctoral student in biology at Caltech and lead author of the study, who
performed the work as a visiting researcher in Parker’s laboratory. They also
worked with Nawroth’s adviser, John Dabiri, a professor of aeronautics and
bioengineering at Caltech, who is an expert in biological propulsion.
“A big goal of our study was to advance tissue
engineering,” says Nawroth. “In many ways, it is still a very qualitative
art, with people trying to copy a tissue or organ just based on what they think
is important or what they see as the major components—without necessarily
understanding if those components are relevant to the desired function or
without analyzing first how different materials could be used.”
It turned out that jellyfish, believed to be the oldest
multi-organ animals in the world, were an ideal subject, as they use muscles to
pump their way through water, and their basic morphology is similar to that of
a beating human heart.
To reverse engineer a medusa jellyfish, the investigators used
analysis tools borrowed from the fields of law enforcement biometrics and
crystallography to make maps of the alignment of subcellular protein networks
within all of the muscle cells within the animal. They then conducted studies
to understand the electrophysiological triggering of jellyfish propulsion and the
biomechanics of the propulsive stroke itself.
Based on such understanding, it turned out that a sheet of
cultured rat heart muscle tissue that would contract when electrically
stimulated in a liquid environment was the perfect raw material to create an
ersatz jellyfish. The team then incorporated a silicone polymer that fashions
the body of the artificial creature into a thin membrane that resembles a small
jellyfish, with eight arm-like appendages.
Using the same analysis tools, the investigators were able to
quantitatively match the subcellular, cellular, and supracellular architecture
of the jellyfish musculature with the rat heart muscle cells.
The artificial construct was placed in container of ocean-like
salt water and shocked into swimming with synchronized muscle contractions that
mimic those of real jellyfish. (In fact, the muscle cells started to contract a
bit on their own even before the electrical current was applied.
“I was surprised that with relatively few components—a silicone
base and cells that we arranged—we were able to reproduce some pretty complex
swimming and feeding behaviors that you see in biological jellyfish,” says
Their design strategy, they say, will be broadly applicable to
the reverse engineering of muscular organs in humans.
“As engineers, we are very comfortable with building things out
of steel, copper, concrete,” says Parker. “I think of cells as another
kind of building substrate, but we need rigorous quantitative design specs to
move tissue engineering to a reproducible type of engineering. The jellyfish
provides a design algorithm for reverse engineering an organ’s function and
developing quantitative design and performance specifications. We can complete
the full exercise of the engineer’s design process: design, build, and test.”
In addition to advancing the field of tissue engineering, Parker
adds that he took on the challenge of building a creature to challenge the
traditional view of synthetic biology which is “focused on genetic
manipulations of cells.” Instead of building just a cell, he sought to “build a
Looking forward, the researchers aim to further evolve the
artificial jellyfish, allowing it to turn and move in a particular direction,
and even incorporating a simple “brain” so it can respond to its environment
and replicate more advanced behaviors like heading toward a light source and
seeking energy or food.
Source: Harvard University