High-Throughput DNA Directed Patterning to Recapitulate Biological Signaling Scenarios (INVITED SPEAKER)

Dissecting the complex action of biological signals that orchestrate single-cell fate decisions as well as tissue function/dysfunction is challenging due to the spatiotemporal parameters modulating their actions. This complexity is further amplified by the fact that these signals— soluble ligands, extracellular matrix-sequestered cues, and cell surface-presented cues—belong to a larger network in which multiple signals are coordinating with each other across time and space. To model and investigate dynamic signaling scenarios in vitro, we have developed a DNA- based patterning platform that enables spatial and temporal control over individual and multivariable signaling scenarios. Our method is based on using photolithography to pattern single-stranded DNA oligonucleotides onto a glass substrate. Complementary oligos, to which cells and ligands have been tagged, hybridize to the patterned oligos. This, in turn, enables the recreation of complex biological signaling environments at both the bulk-tissue and single-cell level with micron-scale control. In this talk, I will discuss in depth our method and highlight a few examples of applications—from stem cell to cancer niches—we have pursued.