Aggregation features of partially unfolded bovine serum albumin modulated by hydrogenated and fluorinated surfactants: Molecular dynamics insights and experimental approaches

Autor(es)

Scanavachi, G. ^[1] ; Espinosa, Y. R. ^[2] ; Yoneda, J. S. ^[1] ; Rial, R. ^[3] ; Ruso, J. M. ^[3] ; Itri, R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Fis, BR-05508090 Sao Paulo - Brazil

^[2] Univ Ind Santander, Grp Bioquim Teor, Cra 27, Calle 9, Bucaramanga - Colombia

^[3] Univ Santiago de Compostela, Dept Appl Phys, Soft Matter & Mol Biophys Grp, Santiago De Compostela - Spain

• Tipo de documento: Artigo Científico
• Fonte: Journal of Colloid and Interface Science; v. 572, p. 9-21, JUL 15 2020.
• Citações Web of Science: 0

Resumo

Protein aggregation plays important roles in life science as, for instance, those associated to neurodegenerative diseases. Although extensive efforts have been done to elucidate all the possible variables related to the aggregation process, much has yet to be done to unveil the main pathways governing protein assembling. In the current work, we induce bovine serum albumin (BSA) association, at pH 3.7, by adding sodium dodecyl sulfate (SDS) and sodium perfluorooctanoate (SPFO) surfactants to BSA solution as promoters of protein aggregation. Firstly, we combine molecular dynamic simulations (MD) to obtain a partially unfolded state of BSA's monomer at the acid pH and small angle X-ray scattering (SAXS) to validate the model. Interestingly, we found by SAXS that at pH 3.7 BSA monomers coexist with dimers in surfactant-free solution. Upon SDS and SPFO addition, the partial unfolded BSA may evolve to large aggregates depending on surfactant concentration. The threshold occurs at 30:1 and 45:1 SDS:BSA and SPFO: BSA molar ratio, respectively, according to turbidity, Thioflavin (ThT) fluorescence, synchrotron radiation circular dichroism (SRCD), SAXS and scanning electron microscopy (SEM) experiments. BSA aggregates are larger in the presence of SDS and structurally more defined upon SPFO binding. Isothermal titration calorimetry (ITC) results give support to infer that both surfactants initially bind to the BSA macromolecule forming a complex. Then, these complexes self-associate towards supramolecular aggregates. Taking into account the physicochemical characteristics of both surfactants and also MD simulations we may suggest that the higher rigidity of the fluorinated chains in respect to hydrogenated ones is crucial to induce more ordered and smaller BSA's aggregates. Our results thus evidence that the ligand structural flexibility might be of a key importance in the pathway of protein aggregation and may pave the way to better understand the early steps of neurodegenerative disorders. (C) 2020 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 18/07194-9 - Hidrogel de G-quadruplex como Potencial Carregador de Fotossensibilizadores para Aplicação em Terapia Fotodinâmica
• Beneficiário: Juliana Sakamoto Yoneda
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado