Dynamics of the formation of a hydrogel by a pathogenic amyloid peptide: islet amyloid polypeptide

Abstract

Many chronic degenerative diseases result from aggregation of misfolded polypeptides to form amyloids. Many amyloidogenic polypeptides are surfactants and their assembly can be catalysed by hydrophobic-hydrophilic interfaces (an air-water interface in-vitro or membranes in-vivo). We recently demonstrated the specificity of surface-induced amyloidogenesis but the mechanisms of amyloidogenesis and more specifically of adsorption at hydrophobic-hydrophilic interfaces remain poorly understood. Thus, it is critical to determine how amyloidogenic polypeptides behave at interfaces. Here we used surface tensiometry, rheology and electron microscopy to demonstrate the complex dynamics of gelation by full-length human islet amyloid polypeptide (involved in type II diabetes) both in the bulk solution and at hydrophobic-hydrophilic interfaces (air-water interface and phospholipids). We show that the hydrogel consists of a 3D supramolecular network of fibrils. We also assessed the role of solvation and dissected the evolution over time of the assembly processes. Amyloid gelation could have important pathological consequences for membrane integrity and cellular functions.

Cu/Zn-superoxide dismutase forms fibrillar hydrogels in a pH-dependent manner via a water-rich extended intermediate state

“…To detect kinetics of physical gel network formation on the macro-scale, rheological measurements such as evolution of Gʹ and Gʹʹ over time, are used because rheology is considered to be the most sensitive method for material characterization compared to chemical analyses [ 49 , 50 ]. Indeed, the rheological kinetic experiments showed that elongated aggregates are formed during the “apparent” lag phase of insulin amyloid gel formation [ 51 ] and the complex dynamics of gelation by islet amyloid polypeptide [ 5 ]. Thus, the measurements of viscoelastic properties of the initial assembly of SOD1 were performed.…”

“…Under certain conditions, fibrous proteins such as gelatin [ 1 ] and fibrils derived from a specific peptide motif such as elastin-like pentapeptides, VPGXG (where X is any residue but proline) [ 2 ] and Ac-C(FKFE) 2 CG-NH 2 [ 3 ] can develop into three-dimensional networks and form hydrogels by self-assembly. Amyloidogenic peptides, such as the β-amyloid diphenylalanine [ 4 ], islet amyloid polypeptide [ 5 ], were also reported to produce viscoelastic hydrogels consisting of fibrillar meshworks. Furthermore, globular proteins, such as insulin [ 6 ], β-lactoglobulin [ 7 , 8 ], bovine serum albumin (BSA) [ 9 ] and α-synuclein [ 10 ] also are known to form hydrogels.…”

The Innovation Comes from the Sea: Chitosan and Alginate Hybrid Gels and Films as Sustainable Materials for Wastewater Remediation

“…In the frequency range selected for both H-Alg/Chito and H-Alg/Chito/BBS, the storage (elastic) modulus G' was always higher than the loss (viscous) one G", meaning that both formulations behave as solid-like gels [58]. The G' and G" moduli for the same sample remained almost parallel for the whole range of angular frequencies investigated, and the absence of a crossover point indicated that gelation was completed in both cases [59]. H-Alg/Chito demonstrated a greater viscous and elastic behaviour than H-Alg/Chito/BBS, suggesting that the addition of BBS-GC influenced the rheological and, consequently, the mechanical properties of the gels.…”

The Physiological and Pathological Implications of the Formation of Hydrogels, with a Specific Focus on Amyloid Polypeptides

“…Thus, it is clear that a relationship between LLPS and hydrogelation, but also between LLPS and amyloid-like formation, exists. As for pathological amyloids, LLPS has been proposed to explain the hydrogelation heterogeneity of islet amyloid polypeptide, and aggregation into pathological amyloids of low-complexity polyglutamine tracts (as found in huntingtin protein involved in Huntington’s disease) is thought to occur by LLPS [ 28 , 43 ].…”

“…Hydrogel-forming natural polymers include proteins (e.g., collagen) and polysaccharides (e.g., starch, chitosan). Although not being universal as some amyloid polypeptides simply precipitate from solution, hydrogel formation has also been reported for a variety of amyloid forming polypeptides, both functional and disease associated [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”