Anomalous Salt Dependence Reveals an Interplay of Attractive and Repulsive Electrostatic Interactions in α-synuclein Fibril Formation

Abstractα-Synuclein (α-syn) is an intrinsically disordered protein with a highly asymmetric charge distribution, whose aggregation is linked to Parkinson’s disease. The effect of ionic strength was investigated at mildly acidic pH (5.5) in the presence of catalytic surfaces in the form of α-syn seeds or anionic lipid vesicles using thioflavin T fluorescence measurements. Similar trends were observed with both surfaces: increasing ionic strength reduced the rate of α-syn aggregation although the surfaces as well as α-syn have a net negative charge at pH 5.5. This anomalous salt dependence implies that short-range attractive electrostatic interactions are critical for secondary nucleation as well as heterogeneous primary nucleation. Such interactions were confirmed in Monte Carlo simulations of α-syn monomers interacting with surface-grafted C-terminal tails, and found to be weakened in the presence of salt. Thus, nucleation of α-syn aggregation depends critically on an attractive electrostatic component that is screened by salt to the extent that it outweighs the screening of the long-range repulsion between negatively charged monomers and negative surfaces. Interactions between the positively charged N-termini of α-syn monomers on the one hand, and the negatively C-termini of α-syn on fibrils or vesicles surfaces on the other hand, are thus critical for nucleation.

Developing an Accurate Heat Transfer Simulation Model of Alaska Pollock Surimi Paste by Estimating the Thermal Diffusivities at Various Moisture and Salt Contents

Alaska pollock (AP) surimi paste was prepared (0–3% salt and 76–84% moisture). The density, specific heat, and thermal conductivity were measured and modelled in temperatures between 25 and 90 °C (R2 > 0.92). The thermal diffusivity (α) function showed a strong dependence on the moisture content and a unique salt dependence at 84% of the moisture content and applied to the heat transfer simulation of surimi paste. The simulation model coupled with the empirical thermal properties accurately predicted the heat penetration curves during heating with RMSE values ranging from 0.43 to 1.22 °C. The salt dependence on thermal diffusivity was identified and modeled only at 84% moisture content. With a model for 84% moisture content, the RMSE value of 3% salt content decreased from 1.11 °C to 0.56 °C. This study demonstrated that an accurate prediction of the heat transfer of the surimi paste needs to be coupled with the nonlinear thermal diffusivity functions.