Unveiling the Role of Surfactants on Amyloid-Like Protein Self-Assembling

ESPINOSA, YANIS R.; RUSO, JUAN; SCANAVACHI, GUSTAVO; ITRI, ROSANGELA

Baltimore, Maryland

Encuentro; 63rd Annual Meeting of The Biophysical Society; 2019

Biophysical Society (BPS)

Some proteins can undergo structural changes that may trigger an aggregation process where they self-assembly into highly ordered aggregates called amyloid fibers. In vivo, these amyloid fibers are related to more than 25 different diseases, some of them are lethal as Creutzfeldt-Jakob disease and others can lead a person to incapacities, as diabetes type II, Alzheimer's and Parkinson's diseases. With the aim of understanding the conditions and mechanisms by which proteins form amyloid fibers, we mixed bovine serum albumin (BSA) at pH 3.7 with sodium dodecyl sulfate (SDS) and sodium perfluorooctanoate (SPFO) to induce the amyloid fibers formation. BSA conformational changes were followed in order to suggest a possible pathway of aggregation. Dynamic Light Scattering (DLS) and Thioflavin T fluorescence data revealed, respectively, the presence of large aggregates and the formation of amyloid-like fibers as the surfactant concentration increased, whereas circular dichroism (CD) showed that BSA second structure changes from α-helix to β-sheet. Transmission electron microscopy (TEM) permitted us to obtain images of fibers and aggregates in the micrometers scale. Further, small angle x-ray scattering (SAXS) measurements provided information about the protein's quaternary structure as a function of surfactant concentration and a more detailed analysis allowed us to suggest a pathway of fibrillation process. Lastly, we performed molecular dynamics (MD) simulations to obtain an all atom structure of BSA at pH 3.7 to study in the molecular level the different effects of SDS or SPFO in the BSA conformation and we also used the MD structures to modeling the SAXS experimental curve.