Protein co-aggregation in systemic amyloidosis studied by isotope-edited infrared spectroscopy.

The aggregation of specific proteins is involved in many diseases, from neurodegenerative disorders to systemic amyloidosis. Increasing evidences from in situ characterizations have pointed out to the crucial role of protein co-aggregation and heterotypic interactions in in vivo aggregation. However, it is very difficult to obtain information on misfolding and aggregation of each protein when more protein variants are co-present in the same mixture. To address this point, an isotope-edited Fourier transform infrared (FTIR) spectroscopy approach will be presented. Since the amide I band in the FTIR spectrum occurs in a different spectral range for ${}^{13}C$ labeled and unlabeled (${}^{12}$C) proteins, the secondary structures (native and $\beta-sheet$ in aggregates) of each species can be monitored when labelled and unlabelled molecules are co-present in a mixture. Not only the misfolding and aggregation of each protein can be monitored independently but also the formation of mixed $\beta$ and unmixed $\beta-sheets$ can be evaluated. The isotope-edited FTIR approach will be illustrated on relevant systems, as the amyloid-like/amorphous aggregation and co-aggregation of proteins involved in systemic amyloidosis.