Prevention and Disintegration of Human Serum Albumin Fibrils under Physiological Conditions: Biophysical Aspects

Abstract

An anomaly in the protein folding process can lead to aggregation or fibrillation of proteins which has been related to neurodegenerative and peripheral diseases. Therefore, it is important to understand the mechanism of prevention of aggregation/fibrillation and to design suitable inhibitors for this process. Literature information suggests that most of the work on these systems has been done on heat induced fibrils (57–65 °C). As a step ahead, in the present study, efforts have been made to understand the inhibition process under physiological conditions (37 °C, pH 7.4), which is more relevant to the fibrils formed under natural cellular environment. The qualitative and quantitative aspects of the interactions of the surfactant sodium dodecyl sulphate (SDS) and antiinflammatory drug diclofenac sodium (DCF) with human serum albumin at different stages of the fibrillation process have been studied employing a combination of spectroscopic, calorimetric, and microscopic techniques. Fibril formation understudied conditions was confirmed by transmission electron microscopy images and thioflavin T binding assay along with dynamic light scattering measurements. Energetics from isothermal titration calorimetry provided insights into the nature of interactions and the mechanism of inhibition. We found inhibition efficiency of the additives in the order, micellar SDS > 45 mM DCF > monomeric SDS > 5 mM DCF. The energetics of interaction, correlated with the molecular structure of inhibitors provides guidelines for effective synthesis and design of inhibitors. ITC results have imparted important relationship between inhibition efficiency and exothermicity of interactions and have demonstrated the significance of polar interactions in fibril prevention by these inhibitors. Interestingly it was found that the micellar SDS not only inhibits the process but also effectively disintegrates the formed fibrils.

Modulation of Surface-Catalyzed Secondary Nucleation during Amyloid Fibrillation of Hen Egg White Lysozyme by Two Common Surfactants

“…40 Mukhija et al recently investigated the effect of SDS on the amyloid fibrillation of human serum albumin (HSA) under physiological conditions and found that the micelle form of SDS could not only inhibit the HSA fibrillation process but also effectively disintegrate HSA fibrils. 27 Ismael et al recently found that SDS can induce amyloid fibrillation of IgG at lower concentrations and inhibit protein aggregation at higher concentrations. 41 In addition, SDS is a well-known surfactant which is able to promote the formation of amyloidbeta oligomer, an intermediate cytotoxic structure during amyloid fibrillation.…”

“…Understanding the modulation factors of amyloid fibrillation is no doubt fundamentally important in amyloid research. − It is not only beneficial to the drug discovery in the treatment and prevention of amyloid-related diseases but also beneficial to the development of amyloid-based novel materials. In this work, we aim to investigate the modulation effect of two common surfactants, sodium dodecyl sulfate (SDS) and Triton X-100 (TX-100), on amyloid fibrillation using hen egg white lysozyme (HEWL) as a model protein.…”

“…Khan et al found that SDS can be an effective amyloid inducer in 25 protein systems by properly controlling solution pH, and they later proposed that protonation was crucial in SDS-induced amyloid fibrillation. , Kumar et al studied the effects of SDS, CTAB, and Triton on the fibrillation kinetics of HEWL and discovered their differential kinetic effects . Mukhija et al recently investigated the effect of SDS on the amyloid fibrillation of human serum albumin (HSA) under physiological conditions and found that the micelle form of SDS could not only inhibit the HSA fibrillation process but also effectively disintegrate HSA fibrils . Ismael et al recently found that SDS can induce amyloid fibrillation of IgG at lower concentrations and inhibit protein aggregation at higher concentrations .…”

Preferential Binding of Thioflavin T to AT-Rich DNA: White Light Emission through Intramolecular Förster Resonance Energy Transfer

“…However, once they get confined within a viscous and restricted environment or in highly ordered nano cavity, radiative transitions are significantly enhanced, thereby suppressing the nonradiative ones and eventually leading to an increase in the fluorescence intensity. , Owing to its unique photophysical properties, over the years ThT has been engaged as a biomarker for the identification of misfolded protein aggregates viz. amyloid fibril − both in “ in vivo ” and “ in vitro ” systems. Recently, it has been reported that ThT can also be used to recognize G-quadruplex and guanine-rich non quadruplex DNA duplex through a turn-on fluorescence mechanism. , However, several research approaches are being presently pursued to establish better insights into the DNA-binding mechanism of ThT for the development of advanced DNA biosensors. − Although there are few reports on the interaction between ThT and dsDNA (calf thymus DNA), there are no comprehensive reports which help us to understand the binding kinetics of ThT with different 20 base pair (bp) long dsDNA having diverse base pair compositions.…”

Mechanistic insights into encapsulation and release of drugs in colloidal niosomal systems: biophysical aspects

“…The protein solutions were subjected to extensive dialysis at 4 °C with a minimum of three changes followed by determining its concentration on a Jasco V-550 double beam spectrophotometer using an extinction coefficient corresponding to A 280 1% = 5.8. 35 The weight measurements were done on a Sartorius BP 211D digital weighing balance with a readability of 0.01 mg.…”