Programming self-organizing multicellular structures with synthetic cell-cell signaling
By S. Toda, Lucas R. Blauch, Sindy K. Y. Tang, Leonardo Morsut, Wendell A. Lim. Science, 2018
404 citations recorded by the source corpus.
Engineering multilayered cellular structures The ability to program the manufacture of biological structures may yield new biomaterials or synthetic tissues and organs. Toda et al. engineered mammalian “sender” and “receiver” cells with synthetic cell surface ligands and receptors that controlled gene regulatory circuits based on Notch signaling. Programming the cells to express cell adhesion molecules and other regulatory molecules enabled spontaneous formation of multilayered structures, like those that form during embryonic development. The three-layered structures even showed regeneration after injury. Science, this issue p. 156 A synthetically engineered signaling system programs cell-cell contact–dependent pattern formation. A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch juxtacrine signaling platform to engineer artificial genetic programs in which specific cell-cell contacts induced changes in cadherin cell adhesion. Despite their simplicity, these minimal intercellular programs were sufficient to yield assemblies with hallmarks of natural developmental systems: robust self-organization into multidomain structures, well-choreographed sequential assembly, cell type divergence, symmetry breaking, and the capacity for regeneration upon injury. The ability of these networks to drive complex structure formation illustrates the power of interlinking cell signaling with cell sorting: Signal-induced spatial reorganization alters the local signals received by each cell, resulting in iterative cycles of cell fate branching. These results provide insights into the evolution of multicellularity and demonstrate the potential to engineer customized self-organizing tissues or materials.
Subfields: Biomedical Engineering, Cell Biology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/41859861192df670349118c904723972bee5180b
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In Biomedical Engineering
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Citations in the corpus
- A scalable pipeline for designing reconfigurable organisms (2020, background): “Applications could be numerous, given the ease of misexpressing novel proteins and synthetic biology pathways and computational circuits in Xenopus cells (27).”