Cell-cell interactions via non-covalent click chemistry.

Area of Science:

• Bioconjugation Chemistry
• Cellular Immunology
• Glycobiology

Background:

• Metabolic glycoengineering allows for the introduction of unnatural sugars onto cell surfaces.
• Bioorthogonal chemistry provides tools for specific and efficient functionalization of these modified cells.
• Targeting cell-cell interactions is crucial for understanding immune responses and developing cancer therapies.

Purpose of the Study:

• To develop a novel method for inducing specific cell-cell adhesion using bioorthogonal chemistry.
• To investigate the potential of engineered cell-cell interactions in activating natural killer (NK) cells against tumor cells.
• To create versatile surface markers for manipulating intercellular communication.

Main Methods:

• Cells were metabolically glycoengineered to display unnatural sugars on their membranes.
• Complementary artificial markers, beta-cyclodextrins (β-CDs) and adamantyl trimers, were conjugated to tumor and T cells, respectively.
• Non-covalent click chemistry was employed to mediate cell-cell adhesion.
• Interleukin-2 (IL-2) production and natural killer (NK) cell-mediated cytolysis were measured.

Main Results:

• Functionalized A459 lung tumor cells and Jurkat T cells exhibited specific adhesion mediated by β-CDs and adamantyl trimers.
• Engineered cell-cell interactions led to increased production of interleukin-2 (IL-2) near cancer cells.
• Natural killer (NK) cells were activated, resulting in the cytolysis of A459 lung tumor cells.

Conclusions:

• This study demonstrates a facile method for engineering cell-cell interactions using metabolic glycoengineering and bioorthogonal chemistry.
• The developed surface markers can be readily applied to various cell types for investigating and manipulating intercellular communication.
• This approach holds promise for enhancing cell-based immunotherapies by promoting targeted immune cell activation and tumor cell killing.