The self-assembly of different cell
types into multicellular structures
and their organization into spatiotemporally controlled patterns are
both challenging and extremely powerful to understand how cells function
within tissues and for bottom-up tissue engineering. Here, we not
only independently control the self-assembly of two cell types into
multicellular architectures with blue and red light, but also achieve
their self-sorting into distinct assemblies. This required developing
two cell types that form selective and homophilic cell–cell
interactions either under blue or red light using photoswitchable
proteins as artificial adhesion molecules. The interactions were individually
triggerable with different colors of light, reversible in the dark,
and provide noninvasive and temporal control over the cell–cell
adhesions. In mixtures of the two cells, each cell type self-assembled
independently upon orthogonal photoactivation, and cells sorted out
into separate assemblies based on specific self-recognition. These
self-sorted multicellular architectures provide us with a powerful
tool for producing tissue-like structures from multiple cell types
and investigate principles that govern them.