Login / Signup

Cell-in-the-loop pattern formation with optogenetically emulated cell-to-cell signaling.

Melinda Liu PerkinsDirk BenzingerMurat ArcakMustafa Khammash
Published in: Nature communications (2020)
Designing and implementing synthetic biological pattern formation remains challenging due to underlying theoretical complexity as well as the difficulty of engineering multicellular networks biochemically. Here, we introduce a cell-in-the-loop approach where living cells interact through in silico signaling, establishing a new testbed to interrogate theoretical principles when internal cell dynamics are incorporated rather than modeled. We present an easy-to-use theoretical test to predict the emergence of contrasting patterns in gene expression among laterally inhibiting cells. Guided by the theory, we experimentally demonstrate spontaneous checkerboard patterning in an optogenetic setup, where cell-to-cell signaling is emulated with light inputs calculated in silico from real-time gene expression measurements. The scheme successfully produces spontaneous, persistent checkerboard patterns for systems of sixteen patches, in quantitative agreement with theoretical predictions. Our research highlights how tools from dynamical systems theory may inform our understanding of patterning, and illustrates the potential of cell-in-the-loop for engineering synthetic multicellular systems.
Keyphrases
  • single cell
  • gene expression
  • cell therapy
  • dna methylation
  • stem cells
  • signaling pathway
  • molecular docking
  • fluorescent probe
  • single molecule
  • visible light