RT Journal Article
T1 Aggregation features of partially unfolded bovine serum albumin modulated by hydrogenated and fluorinated surfactants: Molecular dynamics insights and experimental approaches
A1 Scanavachi, G.
A1 Espinosa, Y. R.
A1 Yoneda, J. S.
A1 Rial Silva, Ramón
A1 Ruso Beiras, Juan Manuel
A1 Itri, R.
K1 Protein aggregation
K1 Serum albumin
K1 Surfactants
K1 Sodium perfluorooctanoate (SPFO)
K1 Sodium dodecyl sulfate (SDS)
K1 SAXS
K1 MD simulation
K1 ITC
AB 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.
PB Elsevier
YR 2020
FD 2020-03-17
LK https://hdl.handle.net/10347/43916
UL https://hdl.handle.net/10347/43916
LA eng
NO Journal of Colloid and Interface Science Volume 572, 15 July 2020, Pages 9-21
NO G. Scanavachi thanks to CAPES support in Brazil and Santander Universidades grant in Spain. The support of Universidad Industrial de Santander to Y.R. Espinosa (Postdoctoral Program Fellowship 2019 - RC N° 022-1577) is gratefully recognized. J.S. Yoneda acknowledges Conselho Nacional de Pesquisa (CNPq, Brazil) for the abroad postdoctoral grant 200390/2014-7 and São Paulo Research Foundation (FAPESP) for the current postdoctoral fellowship (Grant No. 2018/07194-9). J. Ruso and R. Rial thank to Xunta de Galicia (ED41E2018/08). R Itri is recipient from CNPq research fellowship. The authors also thank F. Spinozzi (Universita Politecnica delle Marche, Ancona, Italy) and L. R.S Barbosa (Institute of Physics, USP) for very helpful discussions, and to the LNLS (Campinas, Brazil) for the use of SAXS beamline. Soleil (France) synchrotron for the access to the DISCO beamline during the beamtime granted to Professor B. A. Wallace from Birkbeck College, University of London, is also acknowledged.
DS Minerva
RD 24 abr 2026