Identifying Small Protein Populations by a Combinatorial Fluorescent Molecular Sensor

In recent years, a growing number of cross-reactive sensor arrays that can recognize proteins in a non-selective manner have emerged. Although various differential sensors of this class have been developed and used to discriminate among proteins, these systems are less suitable for analyzing specific populations of proteins in their native environment. Cell-penetrating unimolecular sensors, on the other hand, are very specific and can only detect one target at a time. In this study, we developed a unimolecular sensor that can detect different proteins by generating unique identification patterns, similarly to cross-reactive arrays. We have shown that its unimolecular scaffold and selective binding enable the combinatorial sensor to identify combinations of proteins within complex biological mixtures and track several binding interactions simultaneously.