Light-Controlled Cell-Cell Assembly Using Photocaged Oligonucleotides

The interactions between heterogeneous cell populationsplay importantroles in dictating various cell behaviors. Cell-cell contactmediates communication through the exchange of signaling molecules,electrical coupling, and direct membrane-linked ligand-receptorinteractions. In vitro culturing of multiple cell types with controlover their specific arrangement is difficult, especially in three-dimensional(3D) systems. While techniques that allow one to control the arrangementof cells and direct contact between different cell types have beendeveloped that expand upon simple co-culture methods, specific controlover heterojunctions that form between cells is not easily accomplishedwith current methods, such as 3D cell-printing. In this article, DNA-mediatedcell interactions are combined with cell-compatible photolithographicapproaches to control cell assembly. Specifically, cells are coatedwith oligonucleotides containing DNA nucleobases that are protectedwith photocleavable moieties; this coating facilitated light-controlledcell assembly when these cells were mixed with cells coated with complementaryoligonucleotides. By combining this technology with digital micromirrordevices mounted on a microscope, selective activation of specificcell populations for interactions with other cells was achieved. Importantly,this technique is rapid and uses non-UV light sources. Taken together,this technique opens new pathways for on-demand programming of complexcell structures.