Scaling up self-constructing biological architectures through a novel application of synthetic morphogenesis

Thesis: S.M., Massachusetts Institute of Technology, Department of Architecture, 2018.Thesis: S.M., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2018.Cataloged from PDF version of thesis.Includes bibliographical references (pages 127-131).In this thesis, I introduce a novel biofabrication method Architectures from Staged Self-assembly of Morphogenetic Building Elements (ASSEMBLE), that brings about self-constructing biological structures at the architectural scale by merging scientists' newly developing ability to control the morphogenetic power of living matter with architects' and builders' discrete assembly method, which they have used for centuries to scale up their structures. ASSEMBLE arose from a recognition that in nature, simple building blocks, such as biological cells, self-organize into higher-order, complex structures with no descriptive blueprints at hand and no intelligent designer telling them what to do; instead, they execute a set of generative rules encoded in their DNA. By editing these rules, synthetic biologists can now program living cells to undergo synthetic morphogenesis, and thereby construct higher-order structures by design. However, so far, the biggest programmable structures we have developed in this way are merely on the order of millimeters, which is too small to be relevant in architectural practice. ASSEMBLE bridges this gap by employing these millimeter-scale structures as morphogenetic building elements that can self-assemble with one another through a set of physical assembly cues they are programmed grow on their surfaces. To identify which assembly cues needed on a group of morphogenetic building elements for them to self-assemble into a target structure, I also introduce a 3D global-to-local structural compiler. In this way, ASSEMBLE enables us to create self-constructing architectures by exploiting biological cells as an infinite supply of building material, into which desired structuralby Gizem Gumuskaya.S.M

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

Abstract Fundamental knowledge gaps exist about the plasticity of cells from adult soma and the potential diversity of body shape and behavior in living constructs derived from genetically wild‐type cells. Here anthrobots are introduced, a spheroid‐shaped multicellular biological robot (biobot) platform with diameters ranging from 30 to 500 microns and cilia‐powered locomotive abilities. Each Anthrobot begins as a single cell, derived from the adult human lung, and self‐constructs into a multicellular motile biobot after being cultured in extra cellular matrix for 2 weeks and transferred into a minimally viscous habitat. Anthrobots exhibit diverse behaviors with motility patterns ranging from tight loops to straight lines and speeds ranging from 5–50 microns s−1. The anatomical investigations reveal that this behavioral diversity is significantly correlated with their morphological diversity. Anthrobots can assume morphologies with fully polarized or wholly ciliated bodies and spherical or ellipsoidal shapes, each related to a distinct movement type. Anthrobots are found to be capable of traversing, and inducing rapid repair of scratches in, cultured human neural cell sheets in vitro. By controlling microenvironmental cues in bulk, novel structures, with new and unexpected behavior and biomedically‐relevant capabilities, can be discovered in morphogenetic processes without direct genetic editing or manual sculpting