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bioRxiv · 10.1101/2021.02.05.429999

Mechanically Transduced Immunosorbent Assay To Measure Protein-Protein Interactions

Petell, C. J.·Randene, K.·Pappas, M.·Sandoval, D.·Strahl, B.·Harrison, J. S.·Steimel, J. P.
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Abstract

Measuring protein-protein interaction (PPI) affinities is fundamental to biochemistry. Yet, conventional methods rely upon the law of mass action and cannot measure many PPIs due to a scarcity of reagents and limitations in the measurable affinity ranges. Here we present a novel technique that leverages the fundamental concept of friction to produce a mechanical signal that indicates binding. The mechanically transduced immunosorbent (METRIS) assay utilizes rolling magnetic probes to measure PPI interaction affinities. METRIS measures the translational displacement of protein-coated particles on a protein-functionalized substrate. The translational displacement scales with the effective friction induced by a PPI, thus producing a mechanical signal when a binding event occurs. The METRIS assay uses as little as 20 pmols of reagents to measure a wide range of affinities while exhibiting a high resolution and sensitivity. Here we use METRIS to measure several PPIs that were previously inaccessible using traditional methods, providing new insights into epigenetic recognition.

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Petell, C. J., Randene, K., Pappas, M., Sandoval, D., Strahl, B., Harrison, J. S., Steimel, J. P.. 2021-02-06. Mechanically Transduced Immunosorbent Assay To Measure Protein-Protein Interactions. https://doi.org/10.1101/2021.02.05.429999

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