Using Magnetic Nanoparticles and Protein–Protein Interactions to Measure pH at the Nanoscale

Dynamic magnetization of magnetic nanoparticles provides ready access to passive sensing in nanometer scale environments. Here, we use commercially available streptavidin labeled 100 nm magnetic nanoparticles to develop a nanoscale pH sensor. The sensor works based on pH dependent binding of streptavidin to rat tail type-I collagen. The major protein-protein interactions in this case are well rationalized from zeta potential/mobility measurements, which yield a good measure of the relative pIs of the proteins. The pI is the pH at which the protein has zero overall surface charge. Nanoparticle streptavidin has a stable negative charge over the entire range of the measurements from pH 6 to 7.5 (pI ~2), whereas collagen has a steadily increasing positive charge as the pH drops below 7.5 (pI 7.8). Interactions between protein1 and NP-protein2 based on an initial pI difference allow sophisticated nanoscale sensors to be constructed that respond to small changes in pH via corresponding systematic changes in protein-protein interactions. More generally, any type of protein-protein interaction can in principle be measured using magnetic nanoparticles.