Crosstalk captured between muscles, neural networks in biohybrid machines

March 10, 2020

WASHINGTON, March 10, 2020 -- Scientists watched the formation of a self-emergent machine as stem cell-derived neurons grew toward muscle cells in a biohybrid machine, with neural networks firing in synchronous bursting patterns. The awe-inspiring experiment left them with big questions about the mechanisms behind this growth and a proven method of capturing data for continued study of bioactuators.

In a paper published in APL Bioengineering, from AIP Publishing, the authors were able to capture many of the mechanisms at work where neurons and muscles are cocultured. Using a platform they designed, which holds a suspended neurosphere and several types of muscle cells in different compartments, their work is the first to report a 3D neuromuscular junction in an open platform with multiple muscles.

"The most impactful result is the emergence of a machine where actuators (muscles) emerge from a droplet of a mixture of cell-extracellular matrix, where neurons form a network all by themselves," author Taher Saif said. "It is where neurons reach out to the muscles to form neuromuscular junctions, resulting in a machine that we can operate by shining light, and yet we do not understand with certainty how all of this happened."

Neuromuscular junctions are the source of motor activity, with motor neurons firing to cause muscles to contract. In tiny biorobots using muscle cells as actuators, the ability to tune parameters would allow more precise designs with desirable characteristics and predictable behaviors. Yet, the emerging field of biohybrid robots, including intelligent drug delivery, environment sensing and biohybrid blood circulation pumps, needs proven experimental methods.

"This stage can be compared to the time of Wright brothers trying to fly when potential applications were far and away," Saif said. "The field of biohybrid robots is trying to explore whether machines can at all be made with living cells and scaffolds, what are the scaling laws, and what are the minimum conditions for their emergence."

The authors closely examined the morphology of the neuromuscular units that formed, applied optical stimulation to quantify muscle dynamics, recorded electrical activity of neurospheres and identified mechanisms for modulating bioactuator behavior.

"This is a new design paradigm for biological machines, such as biohybrid robots," Saif said. "Here, the bidirectional interactions emerge and take their own course. If we can understand these interactions, we will be able to guide and modulate them to optimize outcomes, such as high muscle force or synchrony in neuron firing."
The article, "Development of 3D neuromuscular bioactuators," is authored Onur Aydin, Austin P. Passaro, Mohamed Elhebeary, Gelson J. Pagan-Diaz, Anthony Fan, Sittinon Nuethong, Rashid Bashir, Steven L. Stice and M. Taher A. Saif. The article will appear in APL Bioengineering on March 10, 2020 (DOI: 10.1063/1.5134477). After that date, it can be accessed at


APL Bioengineering is an open access journal publishing significant discoveries specific to the understanding and advancement of physics and engineering of biological systems. See

American Institute of Physics

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to