Modular DNA-Origami-Based Nanoarrays Enhance Cell Binding Affinity through the "Lock-and-Key" Interaction

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Biology

Background:

• Cell surface protein recognition via receptor-ligand interactions (RLIs) is crucial for disease diagnosis.
• Nonuniform distribution and complex structures of cell surface proteins limit binding affinity and diagnostic accuracy.
• Existing methods struggle to construct nanotopologies that effectively match membrane protein spatial distributions.

Purpose of the Study:

• To develop advanced DNA-origami-based nanoarrays for enhanced high-affinity cell recognition.
• To engineer nanotopologies that precisely match the spatial distribution of target cell surface proteins.
• To improve the diagnostic capability for diseases, including the detection of circulating tumor cells.

Main Methods:

• Modular DNA origami nanoarrays were constructed with multivalent aptamers.
• Aptamer valency and interspacing were adjusted to create specific nanotopologies.
• The nanoarrays were tested for their ability to recognize target cell clusters and circulating tumor cells.

Main Results:

• The DNA nanoarrays significantly enhanced binding affinity to target cells.
• Nanoarrays demonstrated synergistic recognition of low-affinity antigen-specific cells.
• Clinical detection of circulating tumor cells using DNA nanoarrays confirmed precise recognition and high-affinity RLIs.

Conclusions:

• DNA nanoarrays offer a promising strategy to overcome limitations in cell surface protein recognition.
• Engineered nanotopologies can significantly improve binding affinity and diagnostic sensitivity.
• These DNA nanoarrays have broad potential applications in clinical diagnostics and cell membrane engineering.