A versatile system to record cell-cell interactions.

Area of Science:

• Cell Biology
• Cancer Research
• Biotechnology

Background:

• Cell-cell interactions are crucial for development, homeostasis, and disease, particularly in cancer progression.
• Understanding the cancer microenvironment's role requires methods to record interactions between cancer and stromal cells.

Purpose of the Study:

• To develop a novel system for sensitive and specific labeling of physically interacting cells.
• To facilitate mechanistic studies of cell-cell interactions in various biological contexts, including cancer.

Main Methods:

• Development of GFP-based Touching Nexus (G-baToN) utilizing nanobody-directed fluorescent protein transfer.
• Application of G-baToN for labeling diverse human and mouse cell pairs (e.g., endothelial-pericyte, neuron-astrocyte, cancer-stromal).
• Utilized orthogonal baToN tools for reciprocal labeling, interaction-dependent cargo transfer, and higher-order interaction identification.

Main Results:

• G-baToN enables sensitive and specific physical contact-based labeling across various cell types.
• The system demonstrated generalizability in human and mouse cell models.
• Orthogonal tools allowed for advanced interaction analysis, including reciprocal labeling and cargo transfer.

Conclusions:

• G-baToN is a versatile and sensitive tool for tracking cell-cell interactions.
• This technology will accelerate the understanding of cell-cell communication in cancer and other biological processes.
• The ability to track interacting cells provides new insights into the functional outputs of the cellular microenvironment.