On-Demand Elongation of Peptide Nanofibrils at Cellular Interfaces to Modulate Cell-Cell Interactions

Area of Science:

• Biotechnology
• Cell Biology
• Synthetic Biology

Background:

• Natural cells achieve specific interactions by concentrating binding molecules at contact sites, a capability not yet replicated synthetically.
• Current synthetic methods lack dynamic control over cell-surface interactions, limiting precise cell targeting and manipulation.

Purpose of the Study:

• To engineer responsive peptide fibrils on cell surfaces that selectively elongate upon encountering target cells.
• To develop a dynamic scaffold-based approach for controlled cell-cell interactions, enhancing specificity and adjustability.

Main Methods:

• Constructed responsive peptide fibrils on cell surfaces designed to elongate via strand-displacement reactions triggered by target cell surface molecules.
• Utilized ligands binding to both target and competing cells to achieve region-selective fibril elongation.
• Applied the system to guide natural killer (NK) cells for targeted cancer cell elimination.

Main Results:

• Demonstrated contact-induced, region-selective fibril elongation that selectively promotes host-target cell interactions.
• Successfully guided NK cells to eliminate specific cancer cells through the dynamic scaffold.
• Showcased the system's effectiveness in enhancing specific cell-target interactions.

Conclusions:

• The dynamic scaffold-based approach enables synthetic control over cell-cell interactions, mimicking natural cell behaviors.
• This method broadens the scope of cell combinations for manipulation and enhances the adjustability of cell behaviors.
• Offers a novel strategy for cell-based therapies and biotechnological applications.