Controlled Detachment of Chemically Glued Cells.

We demonstrate a chemically detachable cell-glue system based on linkers containing disulfide bonds as well as functional groups for metabolic glycoengineering and bioorthogonal click chemistry. Azide groups are generated on the cell surface by metabolic glycoengineering, and they are further modified into tetrazine (Tz) or trans-cyclooctene (TCO) using rationally designed cross-linkers. When the Tz-modified and TCO-modified cells are mixed together, cell gluing between these two cell groups is established by Tz-TCO click chemistry. This artificial cell-cell adhesion can be broken by the administration of glutathione (5 mM), which triggers the degradation of disulfide bonds. Both the gluing and detachment processes are rapid (<10 min) and minimally cytotoxic.