The field of morphogenetic engineering was founded in 2009 by René Doursat, who is now a professor at Manchester Metropolitan University doing research in computational biology and bio-inspired computing. Doursat founded the field while at Complex Systems Institute of Paris Ile-de-France (ISC-PIF). Doursat wrote a book called Morphogenetic Engineering, which is co-edited by Hiroki Sayama, professor at Binghamton University, State University of New York and Olivier Michel, Professor at the University of Paris Est - Créteil.
Morphogenetic means relating to morphogenesis. Morphogenesis is the establishment of three-dimensional anatomy, such as during embryonic development where a fertilized egg develops into a complex body pattern through a reliable process of self-assembly. Morphogenetic engineering is an engineering approach that explores the design and implementation of self-organized patterns, morphologies, and architectures in systems comprised of multiple agents such as cells and swarm robots.
Morphogenetic engineering has applications in artificial systems like self-assembling robots, self-coding software, self-constructing buildings, self-reconfiguring production lines, and self-managing energy grids. Applications for morphogenetic engineering are also envisioned in the engineering of tissues, microbial consortia, and living functional materials.
Biological systems that have particularly strong morphogenetic properties are embryogenesis and swarm collaboration in insect colonies. Embryogenesis demonstrates decentralized choreography for self-assembly of complex anatomy. Nest-building insects, such as termites, ants, and wasps, collectively build complicated structures using local coordination rules rather than following an overall blueprint.
While traditional engineering follows a top-down approach where architects plant and build the system, morphogenetic engineering proposes a shift towards the biological paradigm with stages that may be termed “metadesigned development.” Meta-designers would focus on creating local mechanisms or create laws of variation and selection of parameters and then step back and allow components to assemble or coalesce and generate architecture. Morphogenetic engineering falls within the concept of Engineering and Control of Self-Organization (ECSO) and focuses on architectural and complex functional properties of systems and the microlevel influence or programming of these properties.
Embryomorphic engineering, abbreviated EMBENG, is an area of morphogenetic engineering where the spatiotemporal interplay of genetic switches and chemical gradients that create an embryo are abstracted toward artificial systems. In Doursat’s lab, researchers model and simulate principles of self-patterning and self-assembly during embryonic development. An embryomorphic model combines multicellular biological development principles where agents are guided by genetic instructions. Chemical gradient diffusion provides positional information, gene regulation triggers differentiation and patterning, and cell division creates structural constraints.
Doursat’s lab generated a schematic of multiscale and modular distributed processes where each cell contains a gene regulatory network that is modeled as a feed-forward hierarchy of switches that can settle in on or off states. In their 2D EMBENG model, self-assembly is orchestrated by elastic forces and pattern formation by gradient propagation and gene expression. Their Modular Architecture by Programmable Development (3D), abbreviated MAPDEVO, adds the generation of developed organisms that can move by contracting adhesion links between “muscle” cells, and other cells differentiate into “bones” and “joints.”
Researchers from Japan generated quantitative 4D microscopic video data and computational data of the self-assembly process of a neural network based on long-term imaging of the formation of more than a million synaptic connections in the fly visual system. The purpose was to extract principles of neural network self-assembly.
Swarm Intelligence for Morphogenetic Engineering by Bruce J. MacLennan and Allen C. McBride is a book that describes a PDE-based notation for artificial morphogenesis and prototype morphogenetic programming language. The language allows precise description of morphogenetic algorithms and their automatic translation to simulation software.
Morphogenetic engineering of bacterial colonies was performed by a research team lead by Fernan Federici at Pontificia Universidad Catolica de Chile. The group used synthetic biology approaches to engineer symmetry-breaking and domain-specific cell regulation as elementary functions for morphogenetic instructions in bacteria. Symmetry-breaking was based on plasmid segregation. Domain-specific cell regulation acts as artificial cell differentiation by spatial colocalization of ubiquitous and segregated plasmid components.
The basic functions were represented in computational modules they created for CellModeller, a platform that computes growth of rod-shaped bacteria from a single cell to guide the design process. Their computational models and genetic tools allow for prototyping of morphogenetic mechanisms in bacterial colonies. The program allows simulation of internal cells states based on plasmid content and effects of plasmid gene expression.
Morphogenetic micro engineering is derived from morphogenetic engineering and specializes in 3D micro engineered/microfluidic systems to control cell number, position, polarization, migration, and behavior in 3D cell-based models such as embryoid bodies and organoids.
Morphogenetic engineering can refer to the engineering of morphogenesis using genetic techniques. More recently, this engineering discipline, in which cells are genetically engineered to form designed shaped and structures, is termed synthetic morphogenesis. It is a synthetic biology approach to tissue engineering.
One of the goals of stem cell biology is to understand gene regulatory networks and cell-cell interactions for the purpose of engineering of morphogenesis. Tissue engineering and 3D cell culture techniques have been used to produce organoids and other forms of self-organizing tissues, including synthetic mouse embryos. Manipulation of transcription factors, proteins that regulate genes, can be used to induce morphogenesis.
Induction of the GATA6 transcription factor has resulted in formation of the three human germ layers, symmetry breaking and triggered differentiation of endoderm and mesoderm tissue types. GATA6-engineered cells self-organize and self-produce signaling cues for tissue morphogenesis. Synthetic biology approaches could be used to design gene circuits with specific features to induce certain tissue types and perhaps induce angiogenesis or innervation into organoids.
The synthetic Notch system (SynNotch) was developed by Wendell Lim at UC San Francisco and patented to Cell Design Labs. The SynNotch system, based on the Notch cell signaling system, has been used to program cells to self-organize into a two-layered sphere. One group of cells were engineered to express Notch on their surface and another group of cells were engineered with a custom synNotch receptor, which detected Notch on the other cell group. When together, the first cells activated cadherin proteins in the second cells so that they clustered together to form the two-layered sphere. The ability of these spheres to self-repair when damaged was also demonstrated.
