Nature Methods 12, 975–981 (2015)

Credit: NATURE PUBLISHING GROUP

When it comes to the reconstitution of the multicellular architecture of 3D tissues, most culture methods provide limited control over long-range tissue organization. 3D-printing and cell-patterning techniques, such as dielectrophoresis and micromoulding, often have low cell viability and resolution, or suffer from limitations in the solvent conditions and type of extracellular-matrix formulations that can be used. Zev Gartner and colleagues now show how cells and template substrates patterned with complementary DNA can be used to program specific and reversible cell adhesion layer by layer to rapidly build organoid-like microtissues with pre-defined size (up to a few centimetres long), shape and composition, and with control over the tissue's 3D structure with single-cell resolution. Using this modular platform, the researchers built microtissues that combined various cell types with high viability to study the effects of spatial heterogeneity, composition of the extracellular matrix, and tissue shape and size on collective cell behaviour.