Motile Living Biobots Self-Construct from Adult Human Somatic Progenitor Seed Cells

Abstract

AbstractFundamental knowledge gaps exist with respect to the plasticity of cells from adult soma and the potential diversity of body shape and behavior in living constructs derived from such genetically wild-type cells. Here we introduce Anthrobots, a spheroid-shaped multicellular biological robot (biobot) platform with diameters ranging from 30 to 500 microns. Anthrobots have an inherent capacity for motility in aqueous environments, via cilia covering their surface. Each Anthrobot starts out as a single cell, derived from the adult human lung, and self-constructs into a multicellular motile biobot after having been cultured in extra cellular matrix for 2 weeks and transferred into a minimally viscous habitat. Anthrobots exhibit a wide range of behaviors with motility patterns ranging from tight loops to straight lines and speeds ranging from 5-50 microns/second. Our anatomical investigations reveal that this behavioral diversity is significantly correlated with their morphological diversity. Anthrobots can assume diverse morphologies from fully polarized to wholly ciliated bodies with spherical or ellipsoidal shapes, each correlating with a distinct movement type. Remarkably, as a function of these different movement types, Anthrobots were found to be capable of traversing live human tissues in various ways. Furthermore, Anthrobots were able to induce rapid repair of wounds in human neural cell sheets in vitro. By controlling microenvironmental cues in bulk, entirely novel structure, behavior, and biomedically-relevant capabilities can be discovered in morphogenetic processes without direct genetic editing or manual sculpting.Significance StatementWe demonstrate that normal, non-genetically-modified human tracheal cells can be induced to form a new proto-organism - Anthrobots - which exhibit spontaneous behavior, swimming around in one of several patterns, demonstrating plasticity for novel form and function inherent in even elderly human somatic cells. Moreover, Anthrobots are able to traverse over cultured neurons, settling down and causing repair under them: the nerves knit together across the wound gap due to the presence of the Anthrobot. A patient’s own cells can be harnessed to make a motile biological robot that can traverse human tissue and induce repair. In the future, this platform can deliver pro-regenerative therapeutics for a range of biomedical applications that will not trigger rejection or require immune suppression.