Mapping the Broad Structural and Mechanical Properties of Amyloid Fibrils

Abstract

Amyloids are fibrillar nanostructures of proteins that are assembled in several physiological processes in human cells (e.g., hormone storage) but also during the course of infectious (prion) and noninfectious (nonprion) diseases such as Creutzfeldt-Jakob and Alzheimer's diseases, respectively. How the amyloid state, a state accessible to all proteins and peptides, can be exploited for functional purposes but also have detrimental effects remains to be determined. Here, we measure the nanomechanical properties of different amyloids and link them to features found in their structure models. Specifically, we use shape fluctuation analysis and sonication-induced scission in combination with full-atom molecular dynamics simulations to reveal that the amyloid fibrils of the mammalian prion protein PrP are mechanically unstable, most likely due to a very low hydrogen bond density in the fibril structure. Interestingly, amyloid fibrils formed by HET-s, a fungal protein that can confer functional prion behavior, have a much higher Young's modulus and tensile strength than those of PrP, i.e., they are much stiffer and stronger due to a tighter packing in the fibril structure. By contrast, amyloids of the proteins RIP1/RIP3 that have been shown to be of functional use in human cells are significantly stiffer than PrP fibrils but have comparable tensile strength. Our study demonstrates that amyloids are biomaterials with a broad range of nanomechanical properties, and we provide further support for the strong link between nanomechanics and b-sheet characteristics in the amyloid core.

Instantaneous fibrillation of egg white proteome with ionic liquid and macromolecular crowding

“…The stiffness of the fibrils corresponds to a 2-order of magnitude difference in bulk (E′) and loss modulus (E′′) at 25°C ( Supplementary Fig. 37b) 59 . A high value of E′ (42 GPa) was obtained for the fibrils at 25°C, revealing high stiffness.…”

Arrested dynamics in a model peptide hydrogel system

“…The more regular and tightly packed the hydrogen bonds are, the higher E the fiber will have. 63 A rough method of determining the E has been given by Knowles et al, 19 where the E is estimated by a product of the hydrogen bond lengths of within the b-sheet, d b , the hydrogen bond density, z, and a hydrogen bond spring constant, k H . The parameters regarding the geometry of the hydrogen bond have been investigated previously and have been determined to d b = 0.45 nm and z = 1/(0.51 Â 0.35) nm À2 .…”

Design Parameters of Tissue‐Engineering Scaffolds at the Atomic Scale

“…Notably, these results suggest that the higher stability of hydrogels B15/B24 relates to their much higher molecular order observed with ssNMR. Here, the higher bulk mechanical stability of hydrogels B15/B24 likely relates to an optimal molecular packing, maximizing interresidual and intermolecular contacts, while the packing is compromised in disordered samples, which can be associated with reduced mechanical stability . Altogether, we demonstrate that ssNMR, AFM, and rheology provide highly complementary insights at different length scales into the material and functional properties of tissue‐engineering scaffolds.…”