Neuromuscular actuation of biohybrid motile bots

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 40; pp. 19841 - 19847
• Main Authors: Aydin, Onur, Zhang, Xiaotian, Nuethong, Sittinon, Pagan-Diaz, Gelson J., Bashir, Rashid, Gazzola, Mattia, Saif, M. Taher A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 01.10.2019
• Subjects: Actuation; Animals; Axons; Cell Line; Clusters; Coculture Techniques; Collagen - chemistry; Embryonic Stem Cells - cytology; Equipment Design; Extracellular matrix; Flagella; Flagella - physiology; Hydrodynamics; Locomotion; Mice; Motor neurons; Motor Neurons - physiology; Movement; Muscle Contraction; Muscle, Skeletal - physiology; Muscles; Muscular function; Myoblasts; Myoblasts - physiology; Neural stem cells; Neurons; Optogenetics; Physical Sciences; Robotics; Scaffolds; Skeletal muscle; Stem cells; Swimming; Tissues; bioactuator; swimmer; neuromuscular junction; biohybrid system
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1907051116

The integration of muscle cells with soft robotics in recent years has led to the development of biohybrid machines capable of untethered locomotion. A major frontier that currently remains unexplored is neuronal actuation and control of such muscle-powered biohybrid machines. As a step toward this goal, we present here a biohybrid swimmer driven by on-board neuromuscular units. The body of the swimmer consists of a free-standing soft scaffold, skeletal muscle tissue, and optogenetic stem cell-derived neural cluster containing motor neurons. Myoblasts embedded in extracellular matrix self-organize into a muscle tissue guided by the geometry of the scaffold, and the resulting muscle tissue is cocultured in situ with a neural cluster. Motor neurons then extend neurites selectively toward the muscle and innervate it, developing functional neuromuscular units. Based on this initial construct, we computationally designed, optimized, and implemented light-sensitive flagellar swimmers actuated by these neuromuscular units. Cyclic muscle contractions, induced by neural stimulation, drive time-irreversible flagellar dynamics, thereby providing thrust for untethered forward locomotion of the swimmer. Overall, this work demonstrates an example of a biohybrid robot implementing neuromuscular actuation and illustrates a path toward the forward design and control of neuron-enabled biohybrid machines.