Direct Observation of Amyloid Nucleation under Nanomechanical Stretching

Varongchayakul, Nitinun; Johnson, Sara; Quabili, Trina; Cappello, Joseph; Ghandehari, Hamidreza; Solares, Santiago D.; Hwang, Wonmuk; Seog, Joonil

doi:10.1021/nn402322k

Cited by 20 publications

(23 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We hypothesize that the greater force imparted on oligomers, at the bead-water-polystyrene interface, leads to increased fragmentation and subsequent secondary nucleation ( 14 ). Previous studies have shown (at the molecular level) that the fibrillization of proteins can be promoted by imparting mechanical and shear force on existing oligomers ( 53 , 54 , 55 ) (mechanical stress factors have also been identified as risk factors for different types of protein aggregation diseases ( 56 , 57 )). Thus, although this study is performed entirely in vitro and would appear to provide little insight into biological processes of SOD1 aggregation, it establishes the importance of shear force and mechanical stress factors on initiating and propagating SOD1 amyloidogenesis of short fibrils.…”

Section: Discussionmentioning

confidence: 99%

How Do Gyrating Beads Accelerate Amyloid Fibrillization?

Abdolvahabi

Shi

Rasouli

et al. 2017

Biophysical Journal

View full text Add to dashboard Cite

The chemical and physical mechanisms by which gyrating beads accelerate amyloid fibrillization in microtiter plate assays are unclear. Identifying these mechanisms will help optimize high-throughput screening assays for molecules and mutations that modulate aggregation and might explain why different research groups report different rates of aggregation for identical proteins. This article investigates how the rate of superoxide dismutase-1 (SOD1) fibrillization is affected by 12 different beads with a wide range of hydrophobicity, mass, stiffness, and topology but identical diameter. All assays were performed on D90A apo-SOD1, which is a stable and wild-type-like variant of SOD1. The most significant and uniform correlation between any material property of each bead and that bead's effect on SOD1 fibrillization rate was with regard to bead mass. A linear correlation existed between bead mass and rate of fibril elongation (R = 0.7): heavier beads produced faster rates and shorter fibrils. Nucleation rates (lag time) also correlated with bead mass, but only for non-polymeric beads (i.e., glass, ceramic, metallic). The effect of bead mass on fibrillization correlated (R = 0.96) with variations in buoyant forces and contact forces (between bead and microplate well), and was not an artifact of residual momentum during intermittent gyration. Hydrophobic effects were observed, but only for polymeric beads: lag times correlated negatively with contact angle of water and degree of protein adhesion (surface adhesion and hydrophobic effects were negligible for non-polymeric beads). These results demonstrate that contact forces (alone) explain kinetic variation among non-polymeric beads, whereas surface hydrophobicity and contact forces explain kinetic variation among polymeric beads. This study also establishes conditions for high-throughput amyloid assays of SOD1 that enable the control over fibril morphologies and produce eightfold faster lag times and fourfold less stochasticity than in previous studies.

show abstract

Section: Discussionmentioning

confidence: 99%

How Do Gyrating Beads Accelerate Amyloid Fibrillization?

Abdolvahabi

Shi

Rasouli

et al. 2017

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…AFM in particular has been used to investigate the nucleation process of amyloid formation (17,18), fibril assembly, and the topological characteristics and diversity of fibrils (19)(20)(21)(22). Of interest here is the use of AFM to determine the mechanical properties of amyloid fibrils such as persistence length (1,2,4,23), Young's (elastic) modulus (1,5,24), and strength (25).…”

Section: Introductionmentioning

confidence: 99%

Mapping the Broad Structural and Mechanical Properties of Amyloid Fibrils

Lamour

Nassar

Chan

et al. 2017

Biophysical Journal

View full text Add to dashboard Cite

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.

show abstract

“…As discussed above, self-assembly can be induced by a localized mechanical force applied by the AFM tip [15,165,166]. For instance, He et al have shown an interesting in situ AFM based approach to pattern silk fibroin (SF) proteins on surface [15].…”

Section: Other Polymersmentioning

confidence: 99%

“…Seog et al reported a study of silk-elastin-like peptide (SELP), which is another example of mechanically induced self-assembly on surface with possibly a different mechanism [165]. Formation of SELP amyloid fibers was observed after repeated scanning the AFM tip over a single line, which is achieved by disabling the scan in the slow scan direction.…”

Section: Other Polymersmentioning

confidence: 99%

“…They further determined the binding free energy of the C-terminal fragment absorbed to the (100) face of Ca-P using force spectroscopy to reveal mechanisms of shape evolution from spherical particles to elongated nanorods. Seog et al reported a study of silk-elastin-like peptide (SELP), which is another example of mechanically induced self-assembly on surface with possibly a different mechanism [165]. Formation of SELP amyloid fibers was observed after repeated scanning the AFM tip over a single line, which is achieved by disabling the scan in the slow scan direction.…”

Section: Calcium Phosphatementioning

confidence: 99%

See 1 more Smart Citation

In Situ Atomic Force Microscopy Studies on Nucleation and Self-Assembly of Biogenic and Bio-Inspired Materials

Zeng

Vitale-Sullivan

2017

Minerals

View full text Add to dashboard Cite

Through billions of years of evolution, nature has been able to create highly sophisticated and ordered structures in living systems, including cells, cellular components and viruses. The formation of these structures involves nucleation and self-assembly, which are fundamental physical processes associated with the formation of any ordered structure. It is important to understand how biogenic materials self-assemble into functional and highly ordered structures in order to determine the mechanisms of biological systems, as well as design and produce new classes of materials which are inspired by nature but equipped with better physiochemical properties for our purposes. An ideal tool for the study of nucleation and self-assembly is in situ atomic force microscopy (AFM), which has been widely used in this field and further developed for different applications in recent years. The main aim of this work is to review the latest contributions that have been reported on studies of nucleation and self-assembly of biogenic and bio-inspired materials using in situ AFM. We will address this topic by introducing the background of AFM, and discussing recent in situ AFM studies on nucleation and self-assembly of soft biogenic, soft bioinspired and hard materials.

show abstract

Direct Observation of Amyloid Nucleation under Nanomechanical Stretching

Cited by 20 publications

References 104 publications

How Do Gyrating Beads Accelerate Amyloid Fibrillization?

How Do Gyrating Beads Accelerate Amyloid Fibrillization?

Mapping the Broad Structural and Mechanical Properties of Amyloid Fibrils

In Situ Atomic Force Microscopy Studies on Nucleation and Self-Assembly of Biogenic and Bio-Inspired Materials

Contact Info

Product

Resources

About