High-Throughput DNA Directed Patterning to Recapitulate Biological Signaling Scenarios

L. Sohn
University of California, Berkeley,
United States

Keywords: High-Throughput DNA, bio-sensing

Summary:

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