Differential effects of ionic and non-ionic surfactants on lysozyme fibrillation

Abstract

Fibril formation is a common property of many proteins, though not all are associated with diseases. Protein surface charges and the added co-solvents play vital roles in determining fibrillation pathways and kinetics. In order to understand these phenomena, the effects of anionic, cationic and non-ionic surfactants on lysozyme fibrillation were studied. Lysozyme forms fibrils in 2 M and 4 M urea solutions following nucleation-dependent and nucleation-independent pathways, respectively, at neutral pH. Under these conditions, the effects of sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and triton X-100 (Tx) were investigated on the lysozyme structure and fibrillation. The results indicate that there are differential effects of ionic and non-ionic surfactants on fibrillation. In the presence of SDS and CTAB, above their critical micelle concentrations (CMC), lysozyme could not form fibrils. However, non-ionic Tx does not inhibit fibril formation at all concentrations. Note that the time for complete fibril formation is increased by Tx. All of the surfactants are found to increase the initial nucleation phase; however, the extent of increase is less at near the CMC of the ionic surfactants and at above the CMC of Tx. The rates of fibril elongation show varying effects in the presence of different surfactants. The results suggest that the nucleation phase of lysozyme fibrillation is primarily controlled by charge interactions and micellation of the surfactants, but multiple factors might influence the fibril elongation. Furthermore, the surfactants do not alter the fibrillation pathway from nucleation-dependent to nucleation-independent or vice versa in the studied conditions.

Molecular Insight into Human Lysozyme and Its Ability to Form Amyloid Fibrils in High Concentrations of Sodium Dodecyl Sulfate: A View from Molecular Dynamics Simulations

“…Hence, the radius of gyration (Rg) of human lysozyme was also calculated ( Fig 2b ). Previous experimental studies revealed that at temperatures below the thermal denaturation midpoint (Tm) of lysozyme and in the presence of SDS above its CMC, lysozyme maintained its helicity [ 57 ] but not its β-sheet structure [ 46 ]. As shown in Fig 2b , in the SDS 300 K simulation, the Rg was greater than those of the pure water MD simulations at 300 K and 370 K. This could be due to a number of lysozyme secondary structures, such as β-sheet structures, becoming denatured and thereby causing the lysozyme to lose its native compactness.…”

Kinetics of protein fibril formation: Methods and mechanisms

“…Once partially unfolded, fibril-facilitating conformation is attained, the process becomes downhillpolymerization. In such cases, first-order rate equations can be used to calculate the rate of fibril formation [18,50,51]. This assumption has also been used to investigate the effect of mutations and small ions on the rate of fibrillation.…”

Theory of Amyloid Fibril Nucleation from Folded Proteins

“…Urea has a weaker denaturing effect, and does not reach a maximum nucleation rate until the concentration is above 6 M. We note that the two orders of magnitude enhancement between 2 M and 4 M urea (Figure 4) is qualitatively consistent with the observation that the lag time for lysozyme aggregation disappears over this range. [43]…”