Cell-cell interactions via non-covalent click chemistry

Metabolic glycoengineering with unnatural sugars became a valuable tool for introducing recognition markers on the cell membranes via bioorthogonal chemistry. By using this strategy, we functionalized the surface of tumor and T cells using complementary artificial markers based on both beta-cyclodextrins (beta-CDs) and adamantyl trimers, respectively. Once tied on cell surfaces, the artificial markers induced cell-cell adhesion through non-covalent click chemistry. These unnatural interactions between A459 lung tumor cells and Jurkat T cells triggered the activation of natural killer (NK) cells thanks to the increased production of interleukin-2 (IL-2) in the vicinity of cancer cells, leading ultimately to their cytolysis. The ready-to-use surface markers designed in this study can be easily inserted on the membrane of a wide range of cells previously submitted to metabolic glycoengineering, thereby offering a simple way to investigate and manipulate intercellular interactions.

Automated summary

Metabolic glycoengineering with unnatural sugars is used to introduce recognition markers on cell membranes via bioorthogonal chemistry, functionalizing tumor and T cell surfaces. These artificial markers induce cell-cell adhesion and activate natural killer cells, ultimately leading to cancer cell cytolysis. This study's surface markers offer a simple way to investigate and manipulate intercellular interactions on a wide range of cells.