Abstract
Surfactant molecules stimulate amyloid fibrillation and conformational switching in proteins but the mechanisms by which they accomplish these effects are unclear. A cationic gemini surfactant, C16C4C16Br2, with two positively charged heads and two-16C hydrophobic tails induces the amyloid fibrillation of bovine liver catalase (BLC) in vitro at physiological pH. The BLC transformed into amyloid aggregates in the presence of low concentrations (2-150 mu M) of C16C4C16Br2 at pH 7.4, as confirmed by the use of several biophysical techniques (Rayleigh light scattering (RLS), intrinsic fluorescence, thioflavin T fluorescence (ThT), far-UV circular dichroism, and transmission electron microscopy). The secondary structure of BLC also changed according to the concentration of C16C4C16Br2: the alpha-helical structure of BLC decreased in the presence of 2-100 mu M of C16C4C16Br2 but at concentrations above 200 mu M BLC regained a alpha-helical structure very similar to the native BLC. In silico molecular docking between BLC and C16C4C16Br2 suggest that the positively charged heads of the surfactant interact with Asp127 through attractive electrostatic interactions. Moreover, a Pi-cation electrostatic interaction and hydrophobic interactions also take place between the tails of the surfactant and BLC. The stability of the BLC-C16C4C16Br2 complex was confirmed by performing a molecular dynamics simulation and evaluating parameters such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R-g), and solvent accessible surface area (SASA). Apart from its aggregation inducing properties, the gemini surfactant itself causes toxicity to the cancerous cell (A549): which is confirmed by MTT assay. This work delivers new insight into the effect of cationic gemini surfactants in amyloid aggregation and paves the way to the rational design of new anti-amyloidogenic agents.