A morphospace for synthetic organs and organoids: the possible and the actual

Abstract

Efforts in evolutionary developmental biology have shed light on how organs are developed and why evolution has selected some structures instead of others. These advances in the understanding of organogenesis along with the most recent techniques of organotypic cultures, tissue bioprinting and synthetic biology provide the tools to hack the physical and genetic constraints in organ development, thus opening new avenues for research in the form of completely designed or merely altered settings. Here we propose a unifying framework that connects the concept of morphospace (i.e. the space of possible structures) with synthetic biology and tissue engineering. We aim for a synthesis that incorporates our understanding of both evolutionary and architectural constraints and can be used as a guide for exploring alternative design principles to build artificial organs and organoids. We present a three-dimensional morphospace incorporating three key features associated to organ and organoid complexity. The axes of this space include the degree of complexity introduced by developmental mechanisms required to build the structure, its potential to store and react to information and the underlying physical state. We suggest that a large fraction of this space is empty, and that the void might offer clues for alternative ways of designing and even inventing new organs.

Engineering multicellular systems: Using synthetic biology to control tissue self-organization

“…Cells in tissues can be thought of as input-output units capable of concurrent communicate and response generation based on underlying genetic instructions (Fig. 1) [9,17]. Simple rules of communication along with their subsequent activation of functional genes provide the basic routine for emergence of more complex behaviors.…”

Topological analysis of multicellular complexity in the plant hypocotyl

“…These analyses also enable the exploration of extant topological morphospace within plant organs at cellular resolution (Avena-Koenigsberger et al, 2015; Ollé-Vila et al, 2016). These alternative cellular topologies represent additional cellular configurations which are both geometrically and topologically possible, yet most likely compromised in their fitness, and thus function.…”

“…Multicellularity arose multiple times across evolution (Kaiser, 2001; Knoll, 2011), yet how selective pressures shaped and optimized the cellular configurations of these complex assemblies remains poorly understood (Ollé-Vila et al, 2016). Multicellular organs are more than the sum of their cells, and the collective interactions between cells on a global scale confer higher order functionality to the system through a structure-function relationship (Thompson, 1942).…”

Synthetic associative learning in engineered multicellular consortia

“…Extra computational complexity can be achieved by introducing synthetic circuits as part of complex multicellular structures. Such enhanced cognitive complexity might be a desirable trait of future designed organoids and allow a move away from natural design principles [50].…”