An Enzyme‐Responsive Self‐Immolative Recognition Marker for Manipulating Cell–Cell Interactions

Abstract The development of innovative strategies for cell membranes engineering is of prime interest to explore and manipulate cell–cell interactions. Herein, an enzyme‐sensitive recognition marker that can be introduced on cell surface via bioorthogonal chemistry is designed. Once functionalized in this fashion, the cells gain the ability to assemble with cell partners coated with the complementary marker through non‐covalent click chemistry. The artificial cell adhesion induces natural biological processes associated with cell proximity such as inhibiting cancer cell proliferation and migration. On the other hand, the enzymatic activation of the stimuli‐responsive marker triggers the disassembly of cells, thereby restoring the tumor cell proliferation and migration rates. Thus, the study shows that the ready‐to‐use complementary markers are valuable tools for controlling the formation and the breaking of bonds between cells, offering an easy way to investigate biological processes associated to cell proximity.