Two to tango: micropatterned substrates to control cell-cell interactions

Specifying the location of cells with respect to each other is important for cell-based biosensors, tissue engineering, and fundamental questions in cell biology. Cell-substrate interactions can be spatially controlled using a variety of microfabrication- and soft lithography-based approaches; however, because these techniques rely on two-dimensional chemical patterning, they cannot be used to control cell-cell interactions at either the single cell- or tissue-level. By patterning non-adhesive and adhesive gels, we have engineered three-dimensional substrates that can control: 1) the exact location of cell-cell contacts in single cells with micrometer precision, and 2) the final architecture of multi-cellular aggregates. We will demonstrate how these substrates can be used to separate effects due to endothelial cell-cell contact from those due to diffusible, paracrine signaling. In addition, we will show how these techniques can be applied to create tissue constructs and stable, cell-based biosensor platforms.