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 a Nature Biotechnology paper on July 22.
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 lab. 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 Dabiri.
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 beast."
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.
Along with Parker, Nawroth, and Dabiri, contributors to the study
included Hyungsuk Lee, Adam W. Feinberg, Crystal M. Ripplinger, Megan L.
McCain, and Anna Grosberg, all at Harvard.
Journal Reference:
- Janna C Nawroth, Hyungsuk Lee, Adam W Feinberg, Crystal M Ripplinger, Megan L McCain, Anna Grosberg, John O Dabiri, Kevin Kit Parker. A tissue-engineered jellyfish with biomimetic propulsion. Nature Biotechnology, 2012; DOI: 10.1038/nbt.2269
Courtesy: ScienceDaily
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