On Rats (cardiomyocytes) and Jellyfish (bodies)

Here is a recent Nature Biotechnology paper from the researchers at the Wyss Institute (Harvard) and the Dabiri Lab (Caltech) entitled "A tissue-engineered jellyfish with biomimetic propulsion" [1]. The authors of this paper reverse-engineered the essential mechanisms of a muscular pump to create an "artificial" form of jellyfish (Aurelia sp.) called a medusoid [2]. A medusoid (see Figure 1) consists of only a stripped-down version of the jellyfish morphology, replicating only the components needed to approximate jellyfish swimming kinematics [3].

Figure 1. Two examples of a free-swimming medusoid in solution. COURTESY: YouTube video [2].

Once these kinematics were understood, neonatal rat cardiomyocytes [4] were allowed to self-assemble into the desired structure. Cardiomyocytes will spontanously contract in culture, which enabled a cell population to approximate a nerve net. How did they do it? In this post, we will superficially step through the design process and show how the functional morphology of an organism can be engineered. Figure 2 shows the design process.

Figure 1. Steps in the Medusoid design process. COURTESY: Figure 1 (top) in [1].

The first step was abstract design principles from observed jellyfish propulsion. This biomimetic appraoch revealed that motor neurons, striated muscles, and radially-symmetrical appendages are primarily responsible for production of the stroke cycle [5]. The propulsion stroke in Aurelia is produced by two things: a radially symmetric and complete (e.g. power and recovery phases) "bell" contraction [6], and the synchronous activity of a distributed set of pacemakers [7]. In addition, muscle fibers in the jellyfish propulsion mechanism were found to be aligned end-to-end, which provides a mechanism for power production. Once these features were understood, the cellular architecture of the muscles and limbs were mapped using a chemical staining technique. This allowed for millimeter-scale organisms to be created. Morphogenesis was guided using structural (extracellular matrix scaffolding) and chemical (microenvironmental) cues, the results of which can be seen in Figure 3.

Figure 3. Results from the design and bioengineering efforts featured in [1]. COURTESY: Figure 1 (bottom) in [1].

To produce a medusoid body, cardiomyocytes were grown on a PDMS (polymer) scaffold. Because of this, there were constraints in terms of morphological compliance (e.g. bending capacity) [8], which is essential for the organism to initiate and complete its stroke. In the jellyfish, cells assemble around a material called mesoglea, which is a soft substrate supported by stiff ribs. This allows for selective rigidity and the signature bell-shaped contraction (see Figure 4 for comparison of contraction dynamics between Aurelia and the engineered organism).

Figure 4. Comparisons of kinematic performance between the jellyfish and medusoid. COURTESY: Figure 2 in [1].

To solve this design constraint, a lobed design was used. This balances stress generation by a cardiomyocyte population with the bending capacity of the substrate. Since reproducing a stroke-related movement identical to a jellyfish was not possible, a movement that involved a quasi-closed bell being formed at maximal contraction was used instead. These kinematics allowed for muscle fibers to be aligned with respect to the main axis of deformation, which allowed both stress production and substrate bending to be simultaneously maximized.

Figure 5. Evaluating the morphology of jellyfish and medusoids using a vortex flow field. COURTESY: Figure 3 in [1].

Finally, fluid-body interactions were characterized in order to fully optimize the medusoid morphology. These interactions are summarized in Figure 5. According to the authors of this study, the method presented here can be used to design any generalized biomechanical pump. Due to the use of cardiomyocytes, there is no ability to produce multi-stage movement behaviors [9]. However, the use of heterogeneous skeletal muscle fiber populations or transgenic muscle fibers engineered with respect to control of contraction speed may allow for more complicated movement behaviors to be reproduced. It will be interesting to see what types of "hybrid" species (part soft robot, part animal) these and other researchers are able to engineer in the future.

NOTES:

[1] Nawroth, J.C., Lee, H., Feinberg, A.W., Ripplinger, C.M., McCain, M.L., Grosberg, A., Dabiri, J.O., and Parker, K.K.   A tissue-engineered jellyfish with biomimetic propulsion. Nature Biotechnology, 30(8), 792-797 (2012).

[2] YouTube video of "Artificial jellyfish made from rat heart", Nature News. Full article at Nature News.

[3] a strategy similar to that used for designing the PETMAN robot from Boston Dynamics (see picture below). YouTube video here.

[4] for use of this cell type as an experimental model, please see: Chlopcikova, S., Psotova, J.,and Miketova, P.   Neonatal Rat Cardiomyocytes: a model for the study of morphological, biochemical, and electrophysiological characteristics of the heart. Biomedical Papers, 145(2), 49–55 (2001).

Picture of rat cardiomyocytes stained for tropomyosin. COURTESY: Lonza website.

[5] For information on a thermodynamic cycle, please see this. For information on swimming stroke (in humans), please see this.

[6] a "bell" contraction (where all appendages expand outward in the shape of a bell during muscle contraction) can be seen in the far left-hand panel of Figure 1.

[7] For information on cardiac pacemakers, please see this. For in silico simulation of pacemaker neuron dynamics, please see this tutorial from AnimatLab.

Example of a pacemaker cell from the SA node in the human heart. COURTESY: University of Utah Genetic Science Learning Center.

[8] For more information on how compliant substrates are used in soft robotics, please see: Trivedi, D., Rahn, C.D., Kier, W.M., and Walker, I.D.   Soft robotics: Biological inspiration, state of the art, and future research. Applied Bionics and Biomechanics, 5(3), 99–117 (2008).

[9] While these type of movements (e.g. associated with feeding or fighting) may require a central nervous system, they could be approximated using a jellyfish-like nerve net model. For more information on multi-stage movements, please see: Tanji, J.   Sequential Organization of Multiple Movements: involvement of cortical motor areas. Annual Review of Neuroscience, 24, 631–651 (2001).