Rapid generation of hybrid biochemical/mechanical cues in heterogeneous droplets for high-throughput screening of cellular responses

Cells in their native microenvironment are subjected to varying combinations of biochemical cues and mechanical cues in a wide range. Although many signaling pathways have been found to be responsive for extracellular cues, little is known about how biochemical cues crosstalk with mechanical cues in a complex microenvironment. Here, we introduced heterogeneous droplets on a microchip, which were rapidly assembled by combining wettability-patterned microchip and programmed droplet manipulations, for a high-throughput cell screening of the varying combinations of biochemical cues and mechanical cues. This platform constructed a heterogeneous droplet/microgel array with orthogonal gradual chemicals and materials, which was further applied to analyze the cellular Wnt/beta-catenin signaling in response to varying combinations of Wnt ligands and substrate stiffness. Thus, this device provides a powerful multiplexed bioassay platform for drug development, tissue engineering, and stem cell screening.

Automated summary

Cells are influenced by varying combinations of biochemical and mechanical cues in complex microenvironments. This study explores how biochemical cues interact with mechanical cues, by constructing a heterogeneous droplet/microgel array to analyze cell responses to different combinations of Wnt ligands and substrate stiffness. The device provides a powerful multiplexed bioassay platform for drug development, tissue engineering, and stem cell screening.