Sensing metal ions-peptide and protein interfacial interactions

Metal ions play an important role in vital biochemical processes in the human body, interacting with peptides and proteins. It is known that too low as well as too high concentrations of metal ions can cause various health problems, damaging kidneys, bones, and/or the liver. The imbalance of metal ions is also associated with the development of neurodegenerative diseases, such as Alzheimer's and Parkinson's. Therefore, monitoring concentrations of metal ions and understanding their complexation mechanisms with peptides and proteins opens possibilities for early diagnosis and eventually for the development of a cure.
In this work, we first demonstrate how peptides glycyl-glycyl-histidine (GGH) and Oxytocin (OT) can help for the selective detection of metal ions in potentiometric sensing devices. The GGH peptide selectively binds Cu2+ ions, and we investigate in detail the effects of environmental conditions such as electrolyte solution, pH, and the concentration range on the performance of the device. Then, we use the larger peptide OT, which is selective for Cu2+ and Zn2+ ions, for the detection and differentiation of the binding of these two ions in a solution. Finally, we combine atomic force microscopy (AFM), Raman spectroscopy, and molecular dynamic (MD) simulations to characterize the aggregation pathway of alpha-synuclein (αSyn), a protein that plays a key role in the pathogenesis of Parkinson's disease. We found that the presence of Cu2+ ions facilitates the aggregation process. Our measurements were conducted with the purest form of protein in buffer conditions, which can help to understand the aggregation processes happening in the brain in the future by correlating the results with clinical data from patients, obtained from cerebrospinal fluid (CSF) or blood.