Method for rapid mechanical profiling of cells
A high-throughput method to measure cell-generated forces and ligand binding affinity by monitoring the internalization of ruptured DNA tension sensors.
Applications
- Rapid mechanical profiling of cells
- Binding kinetics of mechanotherapies
- CRISPR screening of genes that drive malignant mechanical phenotypes
- Sorting cells with distinct mechanotypes for downstream -omics analysis
- High-throughput screening for cancer metastasis therapies
- Screening of ligands, antibodies, or TCRs for immunotherapies
Technology Overview
This technology allows for the high-throughput measurement of cell adhesion and forces generated by individual cells. It uses HUH-tags to link ligands of choice to DNA probes. Cells plated on the probes rupture fluorescently tagged DNA probes based on cellular forces generated and affinity of ligand-receptor engagement. The assay uses novel readout of ruptured DNA-based tension gauge tethers (TGTs), where the internalized DNA is measured via flow cytometry or next-generation sequencing. This method enables the analysis of heterogeneous cell populations, a significant improvement over existing bead-based systems that cannot be used for large-scale experiments like CRISPR or drug screens.
Phase of Development
TRL: 4-5Active validation and testing with multiple cell lines and ligands. Ligands used so far include multiple recombinant proteins and antibodies. Cell lines include immortalized cell lines, patient derived xenografts, patient derived immune cells.
Desired Partnerships
This technology is now available for:- License
- Sponsored research
- Co-development
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Researchers
- Wendy Gordon, PhD Professor, Department of Biochemistry, Molecular Biology, and Biophysics
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expand_more library_books References (3)
- Matthew R. Pawlak, Adam T. Smiley, Maria Paz Ramirez, Marcus D. Kelly, Ghaidan A. Shamsan, Sarah M. Anderson, Branden A. Smeester, David A. Largaespada, David J. Odde, Wendy R. Gordon (2023), RAD-TGTs: high-throughput measurement of cellular mechanotype via rupture and delivery of DNA tension probes, Nature Communications, 14
- Pawlak, M. R., Gordon, W. R (2025), High-throughput Flow-cytometry Measurement of Cellular Mechanotype Based on Rupture and Delivery of DNA Tension Probes into Cells, Journal of Visualized Experiments, 220
- Matthew R. Pawlak, Andrew M. Baldys, Matthew C. McMahon, Frank M. Cichocki, Wendy R. Gordon (2025), A Generalizable Tension Sensor Platform for Mechanotherapeutic Discovery, bioRxiv
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expand_more cloud_download Supporting documents (1)Product brochureMethod for rapid mechanical profiling of cells.pdf