Light-Controlled Cell-Cell Assembly Using Photocaged Oligonucleotides

The interactions between heterogeneous cell populations play important roles in dictating various cell behaviors. Cell-cell contact mediates communication through the exchange of signaling molecules, electrical coupling, and direct membrane-linked ligand-receptor interactions. In vitro culturing of multiple cell types with control over their specific arrangement is difficult, especially in three-dimensional (3D) systems. While techniques that allow one to control the arrangement of cells and direct contact between different cell types have been developed that expand upon simple co-culture methods, specific control over heterojunctions that form between cells is not easily accomplished with current methods, such as 3D cell-printing. In this article, DNA-mediated cell interactions are combined with cell-compatible photolithographic approaches to control cell assembly. Specifically, cells are coated with oligonucleotides containing DNA nucleobases that are protected with photocleavable moieties; this coating facilitated light-controlled cell assembly when these cells were mixed with cells coated with complementary oligonucleotides. By combining this technology with digital micromirror devices mounted on a microscope, selective activation of specific cell 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 complex cell structures.