Reading conformational changes in proteins with a new colloidal-based interfacial biosensing system

Many biological events such as mutations or aberrant post-translational modifications can alter the conformation and/or folding stability of proteins and their subsequent biological function, which may trigger the onset of diseases like cancer. Evaluating protein folding is hence crucial for the diagnosis of these diseases. Yet, it is still challenging to detect changes in protein folding, especially if they are subtle, in a simple and highly sensitive manner with the current assays. Herein, we report a new colloidal-based interfacial biosensing approach for qualitative and quantitative profiling of various types of changes in protein folding; from denaturation to variant conformations in native proteins, such as protein activation via mutations or phosphorylation. The approach is based on the direct interfacial interaction of proteins freely available in solution with added tannic-acid-capped gold nanoparticles, to interrogate their folding status in their solubilized form. We found that under the optimi...