skip to main content


Title: A cellular platform for the development of synthetic living machines
Robot swarms have, to date, been constructed from artificial materials. Motile biological constructs have been created from muscle cells grown on precisely shaped scaffolds. However, the exploitation of emergent self-organization and functional plasticity into a self-directed living machine has remained a major challenge. We report here a method for generation of in vitro biological robots from frog ( Xenopus laevis ) cells. These xenobots exhibit coordinated locomotion via cilia present on their surface. These cilia arise through normal tissue patterning and do not require complicated construction methods or genomic editing, making production amenable to high-throughput projects. The biological robots arise by cellular self-organization and do not require scaffolds or microprinting; the amphibian cells are highly amenable to surgical, genetic, chemical, and optical stimulation during the self-assembly process. We show that the xenobots can navigate aqueous environments in diverse ways, heal after damage, and show emergent group behaviors. We constructed a computational model to predict useful collective behaviors that can be elicited from a xenobot swarm. In addition, we provide proof of principle for a writable molecular memory using a photoconvertible protein that can record exposure to a specific wavelength of light. Together, these results introduce a platform that can be used to study many aspects of self-assembly, swarm behavior, and synthetic bioengineering, as well as provide versatile, soft-body living machines for numerous practical applications in biomedicine and the environment.  more » « less
Award ID(s):
2020247
NSF-PAR ID:
10357806
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
Science Robotics
Volume:
6
Issue:
52
ISSN:
2470-9476
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. null (Ed.)
    Coordination within and between organisms is one of the most complex abilities of living systems, requiring the concerted regulation of many physiological constituents, and this complexity can be particularly difficult to explain by appealing to physics. A valuable framework for understanding biological coordination is the coordinative structure, a self-organized assembly of physiological elements that collectively performs a specific function. Coordinative structures are characterized by three properties: (1) multiple coupled components, (2) soft-assembly, and (3) functional organization. Coordinative structures have been hypothesized to be specific instantiations of dissipative structures, non-equilibrium, self-organized, physical systems exhibiting complex pattern formation in structure and behaviors. We pursued this hypothesis by testing for these three properties of coordinative structures in an electrically-driven dissipative structure. Our system demonstrates dynamic reorganization in response to functional perturbation, a behavior of coordinative structures called reciprocal compensation. Reciprocal compensation is corroborated by a dynamical systems model of the underlying physics. This coordinated activity of the system appears to derive from the system’s intrinsic end-directed behavior to maximize the rate of entropy production. The paper includes three primary components: (1) empirical data on emergent coordinated phenomena in a physical system, (2) computational simulations of this physical system, and (3) theoretical evaluation of the empirical and simulated results in the context of physics and the life sciences. This study reveals similarities between an electrically-driven dissipative structure that exhibits end-directed behavior and the goal-oriented behaviors of more complex living systems. 
    more » « less
  2. Abstract

    Many organisms utilize group aggregation as a method for survival. The freshwater oligochaete, Lumbriculus variegatus (California blackworms) form tightly entangled structures, or worm “blobs”, that have adapted to survive in extremely low levels of dissolved oxygen (DO). Individual blackworms adapt to hypoxic environments through respiration via their mucous body wall and posterior ciliated hindgut, which they wave above them. However, the change in collective behavior at different levels of DO is not known. Using a closed-loop respirometer with flow, we discover that the relative tail reaching activity flux in low DO is ∼75x higher than in the high-DO condition. Additionally, when flow rate is increased to suspend the worm blobs upward, we find that the average exposed surface area of a blob in low DO is ∼1.4x higher than in high DO. Furthermore, we observe emergent properties that arise when a worm blob is exposed to extreme DO levels. We demonstrate that internal mechanical stress is generated when worm blobs are exposed to high DO levels, allowing them to be physically lifted off from the bottom of a conical container using a serrated endpiece. Our results demonstrate how both collective behavior and the emergent generation of internal mechanical stress in worm blobs change to accommodate differing levels of oxygen. From an engineering perspective, this could be used to model and simulate swarm robots, self-assembly structures, or soft material entanglements.

     
    more » « less
  3. The rise of mobile multi-agent robotic platforms is outpacing control paradigms for tasks that require operating in complex, realistic environments. To leverage inertial, energetic, and cost bene fits of small-scale robots, critical future applications may depend on coordinating large numbers of agents with minimal onboard sensing and communication resources. In this article, we present the perspective that adaptive and resilient autonomous control of swarms of minimal agents might follow from a direct analogy with the neural circuits of spatial cognition in rodents. We focus on spatial neurons such as place cells found in the hippocampus. Two major emergent hippocampal phenomena, self-stabilizing attractor maps and temporal organization by shared oscillations, reveal theoretical solutions for decentralized self-organization and distributed communication in the brain. We consider that autonomous swarms of minimal agents with low-bandwidth communication are analogous to brain circuits of oscillatory neurons with spike-based propagation of information. The resulting notion of `neural swarm control' has the potential to be scalable, adaptive to dynamic environments, and resilient to communication failures and agent attrition. We illustrate a path toward extending this analogy into multi-agent systems applications and discuss implications for advances in decentralized swarm control. 
    more » « less
  4. Biohybrid robots, composed of cellular actuators and synthetic scaffolds, have garnered much attention in recent years owing to the advantages provided by their biological components. In recent years, various forms of biohybrid robots have been developed that are capable of life-like movements, such as walking, swimming, and gripping. Specifically, for walking or crawling biorobots, there is a need for complex functionality and versatile and robust fabrication processes. Here, we designed and fabricated multi-actuator biohybrid walkers with multi-directional walking capabilities in response to noninvasive optical stimulation through a scalable modular biofabrication process. Our new fabrication approach provides a constant mechanical strain throughout the cellular differentiation and maturation process. This maximizes the myotube formation and alignment, limits passive bending, and produces higher active forces. These demonstrations of the new fabrication process and bioactuator designs can pave the way for advanced multi-cellular biohybrid robots and enhance our understanding of the emergent behaviors of these multi-cellular engineered living systems. 
    more » « less
  5. Cannon, William (Ed.)
    Multinucleate cells occur in every biosphere and across the kingdoms of life, including in the human body as muscle cells and bone-forming cells. Data from filamentous fungi suggest that, even when bathed in a common cytoplasm, nuclei are capable of autonomous behaviors, including division. How does this potential for autonomy affect the organization of cellular processes between nuclei? Here we analyze a simplified model of circadian rhythm, a form of cellular oscillator, in a mathematical model of the filamentous fungus Neurospora crassa . Our results highlight a potential role played by mRNA-protein phase separation to keep mRNAs close to the nuclei from which they originate, while allowing proteins to diffuse freely between nuclei. Our modeling shows that syncytism allows for extreme mRNA efficiency—we demonstrate assembly of a robust oscillator with a transcription rate a thousand-fold less than in comparable uninucleate cells. We also show self-organized division of the labor of mRNA production, with one nucleus in a two-nucleus syncytium producing at least twice as many mRNAs as the other in 30% of cycles. This division can occur spontaneously, but division of labor can also be controlled by regulating the amount of cytoplasmic volume available to each nucleus. Taken together, our results show the intriguing richness and potential for emergent organization among nuclei in multinucleate cells. They also highlight the role of previously studied mechanisms of cellular organization, including nuclear space control and localization of mRNAs through RNA-protein phase separation, in regulating nuclear coordination. 
    more » « less