Potential of tetradecyltrimethylammonium bromide in preventing fibrillation/aggregation of lysozyme: biophysical studies.

A key step in the prevention of neurodegenerative disorders is to inhibit protein aggregation or fibrillation process. Functionality recognition is an essential strategy in developing effective therapeutics in addressing the treatment of amyloidosis. Here, we have focused on an approach based on structure-property energetics correlation associated with tetradecyltrimethylammonium bromide (TTAB), a cationic surfactant that acts as an inhibitor targeting different stages of hen egg-white lysozyme fibrillation. Characterization of amyloid fibrils and the inhibitory capability of 16 mM TTAB surfactant on fibrillation were investigated with the calorimetric, spectroscopic and microscopic techniques. ThT binding fluorescence studies inferred that micellar TTAB exerts its maximum inhibitory effect against amyloid fibrillation than monomer TTAB. The TEM measurements also confirmed complete absence of amyloid fibrils at micellar TTAB. At the same time, the transformation of β-sheet to α-helix under the action of TTAB was confirmed by the Far-UV CD spectroscopy. Although there have been some reports suggesting that cationic surfactants can induce aggregation in proteins, this work suggests that polar interactions between head groups of TTAB and amyloid fibrils are the predominant factors that cause retardation in fibrillation by interrupting/disturbing the intermolecular hydrogen bond of β-sheets. The present finding has explored the knowledge-based details in developing efficient potent inhibitors and provides a platform to treat diseases associated with protein misfolding.Communicated by Ramaswamy H. Sarma.