Measuring Weak Protein-Protein Interactions Using a Mechanically Transduced Immunosorbent Assay

Measuring protein-protein interaction (PPI) affinities is fundamental to biochemistry, yet many critical interactions are unmeasurable due to a scarcity of reagents and limitations in the affinity ranges that can be measured. Here, we present a novel technique that leverages the fundamental concept of friction to produce a mechanical signal that correlates to binding potential. 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 the PPI interaction, producing a mechanical signal to indicate binding event. METRIS can measure interactions across a wide range of affinities, $10^{-3}-10^{-15}$M, has high resolution, and measures $\Delta \Delta$G differences of approximately 0.4$\frac{kcal}{mol}$, and utilizes a small amount of reagents, 20 pmol. METTRIS can provides quantitative insights into the interplay between epigentic modifications and can be utilized a new breakthrough in diagnostics.