Patricia F. Fitzpatrick Dimond Ph.D. Technical Editor of Clinical OMICs President of BioInsight Communications

Researchers have created a synthetic “medusoid” that can propel itself in an electrical field in an aqueous environment.

We all marvel at the myriad kinds of jellyfish in aquariums. But few of us come away with the idea that we will go home and build one.

Through computational design and modeling, as well as basic cell biology and biophysiology, a research team from Harvard University and CalTech came up with a jellyfish-resembling synthetic “medusoid”—a synthetic polymer membrane coated with rat cardiac muscle cells that in an aqueous environment can propel itself in an electrical field.

“Morphologically, we’ve built a jellyfish. Functionally, we’ve built a jellyfish. Genetically, this thing is a rat,” said Kit Parker, Ph.D., a biophysicist at Harvard who led the work.

Dr. Parker’s lab works on creating artificial models of human heart tissues for regenerating organs and testing drugs, and the team built the medusoid as a way of understanding the “fundamental laws of muscular pumps. It is an engineer’s approach to basic science: prove that you have identified the right principles by building something with them.”

The aim of the research was to gain new insights into how physiological pumps like the human heart really work. “It occurred to me in 2007 that we might have failed to understand the fundamental laws of muscular pumps,” Dr. Parker explained.

“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.”

In building the medusoid, Dr. Parker and his colleagues collaborated with Janna Naworth, currently a doctoral student in biology at Caltech and lead author of the study, who performed the work as a visiting researcher in Dr. Parker’s lab. They also worked with Naworth’s adviser, John Dabiri, a professor of aeronautics and bioengineering at Caltech and an expert in biological propulsion.

The scientists first studied the alignment of the subcellular protein networks in a jellyfish, and how the animal’s propulsion was triggered by electrophysiological signals as well as the biomechanics of the stroke that propels the animal forward.

The team got muscle power from rat heart muscle cells (cardiomyocytes), cells cultured onto a synthetic polymer that behave similarly to the human variety. Because these cells contract synchronously when electrically stimulated in a liquid environment, they could, the investigators reasoned, create a mechanical propulsion system for the medusoid if grown on an appropriate synthetic matrix.

When placed in a container of ocean-like salt water and shocked into swimming, the medusoid propelled itself with synchronized muscle contractions mimicking those of real jellyfish.

But if this sounds simple, it wasn’t. Nawroth explained to GEN that identification of jellyfish components relevant for swimming and finding suitable bio-engineered “translations” that would function with available materials and fluids presented the biggest challenges in creating the biomechanical construct. In particular, she noted, a biomimetic design, or exact copy of jellyfish components, did not function.

The major problems confronting the scientists, she said, were the differences in material properties and fluid environment. “The silicone rubber is elastic like the jellyfish “jelly” but not compressible. So, we could not use just any jellyfish type as a model, most of which are circular, because a silicone rubber disc does not easily “wrinkle” into a bell.

“We solved this by looking for jellyfish species that avoid compression when contracting, and we found a good solution in the juvenile moon jellyfish, Aurelia aurita.” A moon jelly’s bell consists of a single layer of muscle, with fibers tightly aligned around a central ring and along eight spokes, hence the eight arms in the final design. The lobed geometry of these creatures, she said, allows for compression-free folding into a bell shape, as the arms just tuck inwards.

Finding a fluid environment that would support propulsion dependent on a mammalian cell layer on top of a compressible synthetic polymer proved equally challenging. “Compared to seawater,” she said, the cell culture saline “is warmer and less viscous, providing less ‘stickiness’ to ‘plug’ boundary gaps formed by fluid velocity gradients that extend the effective reach of the arms in the medusoid.”

Overlapping boundary layers close the gaps to oncoming flow, thereby preventing leakage and inefficient fluid transport despite the presence of the gaps. Optimized medusoid body geometry, Nawroth said, favors the formation of boundary layer overlap and thus efficient fluid transport.

“Because of our size, we humans are mostly unaware of the viscosity of water, but for much smaller insects and juvenile jellyfish, water is rather sticky, as is honey for us. For jellyfish-sized constructs such as the medusoid this means that the water surrounding the construct tends to stick to the surface, creating so-called boundary layers. These boundary layers extend the reach of the solid material like the layer of honey that ensheathes the spoon as you pull it out of the jar.”

All of this is important for the design of medusoids because water viscosity—and therefore boundary layer thickness—decreases as temperature increases. “Since the jellyfish swims in 10–20°C water, it can afford to have greater gaps than our construct that swims at 37°C because we use mammalian muscle cells. We had to change the geometry such that the gaps were small enough to be blocked by the thinner boundary layers, while preventing the arms colliding or sticking together.”

The scientists used computational fluid models to simulate the different fluid conditions experienced by the medusoids in culture medium, and to test different medusoid shapes for their propulsion efficiency under these conditions. “We then validated the results empirically by placing different body geometries in a simplified flow field to assess their fluid interactions and proceeded by choosing the optimal geometry for our final medusoid design.”

The medusoid developers, Nawroth said, foresee three major applications for the biomechanical creature including providing a tool for testing the effect of cardiac drugs on pumping performance, either replacing or complementing animal experiments. It may also serve as a model for rational, systematic design of tissue-engineered organs to potentially replace organ transplants, as well as a model for testing animal/organ anatomies that are not present in nature.

And the team has ambitions beyond the current medusoid model. At this stage, they say, the medusoid’s swimming behavior is limited to exactly one stereotypic mode. They want to build a better jellyfish, potentially integrating multiple cell types and materials into the design that will allow the constructs to sense and respond to the environment, perhaps employing internal decision-making circuits to choose a suitable response from a variety of behaviors.

Patricia F. Dimond, Ph.D. ([email protected]), is a principal at BioInsight Consulting.

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