Effects of sedimentation, microgravity, hydrodynamic mixing and air–water interface on α-synuclein amyloid formation

Abstract

A comprehensive analysis on the impact of sedimentation, microgravity hydrodynamic mixing and air–water interface on α-synuclein aggregation kinetics.

Environmental Control of Amyloid Polymorphism by Modulation of Hydrodynamic Stress

“…By contrast, the slower static S-bubble condition (Figure 2d and purple boxes in Figure 2e−g) showed the abundant formation of only protofibrillar aggregates (height of peaking 3.1 ± 0.2 nm) after 30 days, 30,34 and only after 55 days we had the formation of an abundant population of mature amyloid fibrils with an average height of 5.2 ± 0.4 nm (Figures S6 and S7).…”

“…We then plotted the intensity of ThT fluorescence versus the CD intensity at 218 nm (Figure 1i) to confirm the tendency of protein aggregate formation in both conditions of high and low hydrodynamic environmental stress. 34 Single Aggregate Characterization of α-Syn Amyloid Formation. The morphological differences of amyloid aggregates play a critical role in determining various biological activities, e.g., cytotoxicity, 12,14 and biomaterial performance such as mechanical properties.…”

“…26,27 It was previously suggested that the interplay among amyloid polymorphs can be controlled by intrinsic kinetics parameters 28 and induce amyloid polymorphs. 8,9,29 Furthermore, extrinsic factors, such as hydrophobic air−water interfaces, 30−32 have shown to significantly accelerate primary nucleation, 30,33,34 which may impact the morphology of protein aggregates. 25,30,32,35 Similarly, the presence of hydrodynamic flows strongly influences aggregation kinetics by promoting secondary nucleation 33,34,36 and protein−protein interaction, 26,36−38 suggesting a further influence on fibrillar polymorphism.…”

“…8,9,29 Furthermore, extrinsic factors, such as hydrophobic air−water interfaces, 30−32 have shown to significantly accelerate primary nucleation, 30,33,34 which may impact the morphology of protein aggregates. 25,30,32,35 Similarly, the presence of hydrodynamic flows strongly influences aggregation kinetics by promoting secondary nucleation 33,34,36 and protein−protein interaction, 26,36−38 suggesting a further influence on fibrillar polymorphism. Hydrodynamic and interfacial effects often show a synergetic impact in many physiological circumstances, 33,39,40 such as bloodstream to cerebrovascular system.…”

Amyloid Formation in Nanoliter Droplets

“…By this deformation, a surface tension gradient can be formed on the droplet surface. This gradient induces the Marangoni effect, whereby unfolded peptide chains are locally deposited at the edge and form a relatively high local concentration [ 20 , 21 ]. Owing to the significant molecular crowding at the corner, rapid nucleation was observed, as shown by the results of bright-field and fluorescence microscopies ( Figure 4 b,c, respectively).…”