Neuromuscular actuation of biohybrid motile bots

Abstract

Significance Biohybrid machines have been developed using muscles to actuate soft robotic structures. We envision that the integration of neurons into the embodiment of such systems can transform them into intelligent machines which, for instance, could use sensory neurons to detect environmental cues then adaptively respond and orchestrate various motor patterns through their neural circuitry. However, achieving such sensory-motor modalities relies on the ability of neural units to command muscle activity, making actuation through motor neurons the first milestone. Here, we achieve this milestone and demonstrate neuromuscular actuation of a biohybrid swimmer. This paves the way for the development of biohybrid embodied platforms as models to gain deeper understanding of motor control, with potentially broad impact in robotics, bioengineering, and health. 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.