Interactions between a luminescent conjugated oligoelectrolyte and insulin during early phases of amyloid formation

Folding of an amino acid polypeptide chain into its native three-dimensional protein is a delicate process. Misfolding may cause assembly of dysfunctional proteins leading to aggregated assemblies, in medicine denoted amyloids, causing Alzheimer’s, Parkinson and a number of other protein related diseases. Amyloids have also shown promising results as building blocks in organic electronic applications, associated to conjugated polymers. Luminescent conjugated oligo- and polythiophenes (LCPs) have been further developed for biosensor applications exhibiting good ability to discriminate and determine different types of amyloid enrichment in complex environments, such as in tissue sections. The nature of interaction between the amyloid assemblies and LCPs is still not fully understood. In this study we use steady-state fluorescence spectroscopy, dynamic light scattering, transmission electron microscopy and fluorescence correlation spectroscopy to follow the interplay between the anionic oligothiophene derivative 4',3'''-Bis-carboxymethyl-[2,2';5',2'';5'',2''';5''',2'''']quinque thiophene-5,5''''-dicarboxylic acid (p-FTAA), and prefibrillar protein assemblies present during the earlier stage of in vitro fibrillation of bovine insulin. Our findings confirm that p-FTAA interacts with pre-fibrillar species of insulin preceding the formation of mature insulin amyloid fibrils, and insights regarding the molecular interplay between p-FTAA and these species are provided.Funding Agencies|Swedish Science Council (VR)||Strategic Research Foundation (SSF) through the center for organic bioelectronics (OBOE)||Knut and Alice Wallenberg foundation|