PT  - JOURNAL ARTICLE
AU  - Melinda Liu Perkins
AU  - Dirk Benzinger
AU  - Murat Arcak
AU  - Mustafa Khammash
TI  - Cell-in-the-loop pattern formation with optogenetically emulated cell-to-cell signaling
AID  - 10.1101/679597
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 679597
4099  - http://biorxiv.org/content/early/2019/06/22/679597.short
4100  - http://biorxiv.org/content/early/2019/06/22/679597.full
AB  - Designing and implementing synthetic biological pattern formation remains a challenge due to underlying theoretical complexity as well as the difficulty of engineering multicellular networks bio-chemically. 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 a theory that offers an easy-to-use test to predict the emergence of contrasting patterns in gene expression among laterally inhibiting cells. Guided by the theory, we experimentally demonstrated spontaneous checkerboard patterning in an optogenetic setup where cell-to-cell signaling was emulated with light inputs calculated in silico from real-time gene expression measurements. The scheme successfully produced 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.